Clinical Topics & News

Although teledermatology utilization in the United States traditionally has lagged behind other countries,^1,2 the COVID-19 pandemic upended this trend by creating the need for a massive teledermatology experiment. Recently reported survey results from a large representative sample of US dermatologists (5000 participants) on perceptions of teledermatology during COVID-19 indicated that only 14.1% of participants used teledermatology prior to the COVID-19 pandemic vs 54.1% of dermatologists in Europe.^2,3 Since the pandemic started, 97% of US dermatologists reported teledermatology use,³ demonstrating a huge shift in utilization. This trend is notable, as teledermatology has been shown to increase access to dermatology in underserved areas, reduce patient travel times, improve patient triage, and even reduce carbon footprints.^1,4 Thus, to sustain the momentum, insights from the recent teledermatology experience during the pandemic should inform future development.

Notably, the COVID-19 pandemic led to a rapid shift in focus from store-and-forward teledermatology to live video–based models.^1,2 Logistically, live video visits are challenging, require more time and resources, and often are diagnostically limited, with concerns regarding technology, connectivity, reimbursement, and appropriate use.³ Prior to COVID-19, formal Health Insurance Portability and Accountability Act–compliant teledermatology platforms often were costly to establish and maintain, largely relegating use to academic centers and Veterans Affairs hospitals. Thus, many fewer private practice dermatologists had used teledermatology compared to academic dermatologists in the United States (11.4% vs 27.6%).³ Government regulations—a key barrier to the adoption of teledermatology in private practice before COVID-19—were greatly relaxed during the pandemic. The Centers for Medicare and Medicaid Services removed restrictions on where patients could be seen, improved reimbursement for video visits, and allowed the use of platforms that are not Health Insurance Portability and Accountability Act compliant. Many states also relaxed medical licensing rules.

Overall, the general outlook on telehealth seems positive. Reimbursement has been found to be a primary factor in dermatologists’ willingness to use teledermatology.³ Thus, sustainable use of teledermatology likely will depend on continued reimbursement parity for live video as well as store-and-forward consultations, which have several advantages but currently are de-incentivized by low reimbursement. The survey also found that 70% of respondents felt that teledermatology use will continue after COVID-19, while 58% intended to continue use—nearly 5-fold more than before the pandemic.³ We suspect the discrepancy between participants’ predictions regarding future use of teledermatology and their personal intent to use it highlights perceived barriers and limitations of the long-term success of teledermatology. Aside from reimbursement, connectivity and functionality were common concerns, emphasizing the need for innovative technological solutions.³ Moving forward, we anticipate that dermatologists will need to establish consistent workflows to establish consistent triage for the most appropriate visit—in-person visits vs teledermatology, which may include augmented, intelligence-enhanced solutions. Similar to prior clinician perspectives about which types of visits are conducive to teledermatology,² most survey participants believed virtual visits were effective for acne, routine follow-ups, medication monitoring, and some inflammatory conditions.³

Importantly, we must be mindful of patients who may be left behind by the digital divide, such as those with lack of access to a smartphone or the internet, language barriers, or limited telehealth experience.⁵ Systems should be designed to provide these patients with technologic and health literacy aid or alternate modalities to access care. For example, structured methods could be introduced to provide training and instructions on how to access phone applications, computer-based programs, and more. Likewise, for those with hearing or vision deficits, it will be important to improve sound amplification and accessibility for headphones or hearing aid connectivity, as well as appropriate font size, button size, and application navigation. In remote areas, existing clinics may be used to help field specialty consultation teleconferences. Certainly, applications and platforms devised for teledermatology must be designed to serve diverse patient groups, with special consideration for the elderly, those who speak languages other than English, and those with disabilities that may make telehealth use more challenging.

Large-scale regulatory changes and reimbursement parity can have a substantial impact on future teledermatology use. Advocacy efforts continue to push for fair valuation of telemedicine, coverage of store-and-forward teledermatology codes, and coverage for all models of care. It is imperative for the dermatology community to continue discussions on implementation and methodology to best leverage this technology for the most patient benefit.

Although teledermatology utilization in the United States traditionally has lagged behind other countries,^1,2 the COVID-19 pandemic upended this trend by creating the need for a massive teledermatology experiment. Recently reported survey results from a large representative sample of US dermatologists (5000 participants) on perceptions of teledermatology during COVID-19 indicated that only 14.1% of participants used teledermatology prior to the COVID-19 pandemic vs 54.1% of dermatologists in Europe.^2,3 Since the pandemic started, 97% of US dermatologists reported teledermatology use,³ demonstrating a huge shift in utilization. This trend is notable, as teledermatology has been shown to increase access to dermatology in underserved areas, reduce patient travel times, improve patient triage, and even reduce carbon footprints.^1,4 Thus, to sustain the momentum, insights from the recent teledermatology experience during the pandemic should inform future development.

Notably, the COVID-19 pandemic led to a rapid shift in focus from store-and-forward teledermatology to live video–based models.^1,2 Logistically, live video visits are challenging, require more time and resources, and often are diagnostically limited, with concerns regarding technology, connectivity, reimbursement, and appropriate use.³ Prior to COVID-19, formal Health Insurance Portability and Accountability Act–compliant teledermatology platforms often were costly to establish and maintain, largely relegating use to academic centers and Veterans Affairs hospitals. Thus, many fewer private practice dermatologists had used teledermatology compared to academic dermatologists in the United States (11.4% vs 27.6%).³ Government regulations—a key barrier to the adoption of teledermatology in private practice before COVID-19—were greatly relaxed during the pandemic. The Centers for Medicare and Medicaid Services removed restrictions on where patients could be seen, improved reimbursement for video visits, and allowed the use of platforms that are not Health Insurance Portability and Accountability Act compliant. Many states also relaxed medical licensing rules.

Overall, the general outlook on telehealth seems positive. Reimbursement has been found to be a primary factor in dermatologists’ willingness to use teledermatology.³ Thus, sustainable use of teledermatology likely will depend on continued reimbursement parity for live video as well as store-and-forward consultations, which have several advantages but currently are de-incentivized by low reimbursement. The survey also found that 70% of respondents felt that teledermatology use will continue after COVID-19, while 58% intended to continue use—nearly 5-fold more than before the pandemic.³ We suspect the discrepancy between participants’ predictions regarding future use of teledermatology and their personal intent to use it highlights perceived barriers and limitations of the long-term success of teledermatology. Aside from reimbursement, connectivity and functionality were common concerns, emphasizing the need for innovative technological solutions.³ Moving forward, we anticipate that dermatologists will need to establish consistent workflows to establish consistent triage for the most appropriate visit—in-person visits vs teledermatology, which may include augmented, intelligence-enhanced solutions. Similar to prior clinician perspectives about which types of visits are conducive to teledermatology,² most survey participants believed virtual visits were effective for acne, routine follow-ups, medication monitoring, and some inflammatory conditions.³

Importantly, we must be mindful of patients who may be left behind by the digital divide, such as those with lack of access to a smartphone or the internet, language barriers, or limited telehealth experience.⁵ Systems should be designed to provide these patients with technologic and health literacy aid or alternate modalities to access care. For example, structured methods could be introduced to provide training and instructions on how to access phone applications, computer-based programs, and more. Likewise, for those with hearing or vision deficits, it will be important to improve sound amplification and accessibility for headphones or hearing aid connectivity, as well as appropriate font size, button size, and application navigation. In remote areas, existing clinics may be used to help field specialty consultation teleconferences. Certainly, applications and platforms devised for teledermatology must be designed to serve diverse patient groups, with special consideration for the elderly, those who speak languages other than English, and those with disabilities that may make telehealth use more challenging.

Large-scale regulatory changes and reimbursement parity can have a substantial impact on future teledermatology use. Advocacy efforts continue to push for fair valuation of telemedicine, coverage of store-and-forward teledermatology codes, and coverage for all models of care. It is imperative for the dermatology community to continue discussions on implementation and methodology to best leverage this technology for the most patient benefit.

Although teledermatology utilization in the United States traditionally has lagged behind other countries,^1,2 the COVID-19 pandemic upended this trend by creating the need for a massive teledermatology experiment. Recently reported survey results from a large representative sample of US dermatologists (5000 participants) on perceptions of teledermatology during COVID-19 indicated that only 14.1% of participants used teledermatology prior to the COVID-19 pandemic vs 54.1% of dermatologists in Europe.^2,3 Since the pandemic started, 97% of US dermatologists reported teledermatology use,³ demonstrating a huge shift in utilization. This trend is notable, as teledermatology has been shown to increase access to dermatology in underserved areas, reduce patient travel times, improve patient triage, and even reduce carbon footprints.^1,4 Thus, to sustain the momentum, insights from the recent teledermatology experience during the pandemic should inform future development.

Notably, the COVID-19 pandemic led to a rapid shift in focus from store-and-forward teledermatology to live video–based models.^1,2 Logistically, live video visits are challenging, require more time and resources, and often are diagnostically limited, with concerns regarding technology, connectivity, reimbursement, and appropriate use.³ Prior to COVID-19, formal Health Insurance Portability and Accountability Act–compliant teledermatology platforms often were costly to establish and maintain, largely relegating use to academic centers and Veterans Affairs hospitals. Thus, many fewer private practice dermatologists had used teledermatology compared to academic dermatologists in the United States (11.4% vs 27.6%).³ Government regulations—a key barrier to the adoption of teledermatology in private practice before COVID-19—were greatly relaxed during the pandemic. The Centers for Medicare and Medicaid Services removed restrictions on where patients could be seen, improved reimbursement for video visits, and allowed the use of platforms that are not Health Insurance Portability and Accountability Act compliant. Many states also relaxed medical licensing rules.

Overall, the general outlook on telehealth seems positive. Reimbursement has been found to be a primary factor in dermatologists’ willingness to use teledermatology.³ Thus, sustainable use of teledermatology likely will depend on continued reimbursement parity for live video as well as store-and-forward consultations, which have several advantages but currently are de-incentivized by low reimbursement. The survey also found that 70% of respondents felt that teledermatology use will continue after COVID-19, while 58% intended to continue use—nearly 5-fold more than before the pandemic.³ We suspect the discrepancy between participants’ predictions regarding future use of teledermatology and their personal intent to use it highlights perceived barriers and limitations of the long-term success of teledermatology. Aside from reimbursement, connectivity and functionality were common concerns, emphasizing the need for innovative technological solutions.³ Moving forward, we anticipate that dermatologists will need to establish consistent workflows to establish consistent triage for the most appropriate visit—in-person visits vs teledermatology, which may include augmented, intelligence-enhanced solutions. Similar to prior clinician perspectives about which types of visits are conducive to teledermatology,² most survey participants believed virtual visits were effective for acne, routine follow-ups, medication monitoring, and some inflammatory conditions.³

Importantly, we must be mindful of patients who may be left behind by the digital divide, such as those with lack of access to a smartphone or the internet, language barriers, or limited telehealth experience.⁵ Systems should be designed to provide these patients with technologic and health literacy aid or alternate modalities to access care. For example, structured methods could be introduced to provide training and instructions on how to access phone applications, computer-based programs, and more. Likewise, for those with hearing or vision deficits, it will be important to improve sound amplification and accessibility for headphones or hearing aid connectivity, as well as appropriate font size, button size, and application navigation. In remote areas, existing clinics may be used to help field specialty consultation teleconferences. Certainly, applications and platforms devised for teledermatology must be designed to serve diverse patient groups, with special consideration for the elderly, those who speak languages other than English, and those with disabilities that may make telehealth use more challenging.

Large-scale regulatory changes and reimbursement parity can have a substantial impact on future teledermatology use. Advocacy efforts continue to push for fair valuation of telemedicine, coverage of store-and-forward teledermatology codes, and coverage for all models of care. It is imperative for the dermatology community to continue discussions on implementation and methodology to best leverage this technology for the most patient benefit.

Since the end of 2019, COVID-19 infection caused by SARS-CoV-2 has spread in a worldwide pandemic. The first cutaneous manifestations possibly linked to COVID-19 were reported in spring 2020.¹ Herpes zoster (HZ) was suspected as a predictive cutaneous manifestation of COVID-19 with a debated prognostic significance.² The end of 2020 was marked with the beginning of vaccination against COVID-19, and safety studies reported few side effects after vaccination with nucleoside-modified messenger RNA (mRNA) COVID-19 vaccines.³ Real-life use of vaccines could lead to the occurrence of potential side effects (or fortuitous medical events) that were not observed in these studies. We report a series of 5 cases of HZ occurring after vaccination with a nucleoside-modified mRNA COVID-19 vaccine extracted from a declarative cohort of cutaneous reactions in our vaccination center.

Case Series

We identified 2 men and 3 women (Table) who experienced HZ after vaccination with a nucleoside-modified mRNA COVID-19 vaccine (Comirnaty, Pfizer-BioNTech). Patients fulfilled French governmental criteria for vaccination at the time of the report—older than 75 years or a health care professional—and they were vaccinated at the vaccination center of a French university hospital. The median age of the patients was 56 years (interquartile range [IQR], 51–82 years). One patient was diagnosed with COVID-19 in February 2020. A medical history of HZ was found in 1 patient. No medical history of immunosuppression was noted. Herpes zoster was observed on the same side of the body as the vaccination site in 4 patients. The median delay before the onset of symptoms was 6 days (IQR, 1–15 days) after injection. The median duration of the symptoms was 13 days (IQR, 11.5–16.5 days). Clinical signs of HZ were mild with few vesicles in 4 patients, and we observed a notably long delay between the onset of pain and the eruption of vesicles in 2 cases (4 and 10 days, respectively). The clinical diagnosis of HZ was confirmed by a dermatologist for all patients (Figures 1 and 2). Polymerase chain reaction assays for the detection of the varicella-zoster virus were performed in 2 cases and were positive. A complete blood cell count was performed in 1 patient, and we observed isolated lymphopenia (500/mm³ [reference range, 1000–4000/mm³]). Herpes zoster occurred after the first dose of vaccine in 4 patients and after the second dose for 1 patient. Three patients were treated with antiviral therapy (acyclovir) for 7 days. Three patients recovered from symptoms within 2 weeks and 2 patients within 1 week.

Comment

We report a series of HZ cases occurring after vaccination with a nucleoside-modified mRNA COVID-19 vaccine. We did not observe complicated HZ, and most of the time, HZ lesions were located on the same side of the body as the vaccine injection. One case of HZ after COVID-19 vaccination was reported by Bostan and Yalici-Armagan,⁴ but it followed injection with an inactivated vaccine, which is different from our series. Herpes zoster remains rarely reported, mainly following mRNA COVID-19 vaccination.⁵

Cases of HZ after vaccination have been reported after the live attenuated zoster or yellow fever vaccines, but HZ should not appear as a concomitant effect after any type of vaccines.^6,7 Kawai et al⁸ reported that the incidence rate of HZ ranged from 3 to 5 cases per 1000 person-years in North America, Europe, and Asia-Pacific. The risk for recurrence of HZ ranged from 1% to 6% depending on the type of study design, age distribution of studied populations, and definition.⁸ In another retrospective database analysis in Israel, the incidence density rate of HZ was 3.46 cases per 1000 person-years in the total population and 12.8 cases per 1000 person-years in immunocompromised patients, therefore the immunocompromised status is important to consider.⁹

In our declarative cohort of skin eruptions before vaccination, we recorded 11 cases of HZ among 148 skin eruptions (7.43%) at the time of the study, but the design of the study did not allow us to estimate the exact incidence of HZ in the global COVID-19–vaccinated population because our study was not based on a systematic and prospective analysis of all vaccinated patients. The comparison between the prevalence of HZ in the COVID-19–vaccinated population and the nonvaccinated population is difficult owing to the lack of data about HZ in the nonvaccinated population at the time of our analysis. Furthermore, we did not include all vaccinated patients in a prospective follow-up. We highlight the importance of medical history of patients that differed between vaccinated patients (at the time of our analysis) and the global population due to French governmental access criteria to vaccination. The link to prior SARS-CoV-2 infection was uncertain because a medical history of COVID-19 was found in only 1 patient. Only 1 patient had a history of HZ, which is not a contraindication of COVID-19 vaccination.

Postinjection pains are frequent with COVID-19 vaccines, but clinical signs such as extension of pain, burning sensation, and eruption of vesicles should lead the physician to consider the diagnosis of HZ, regardless of the delay between the injection and the symptoms. Indeed, the onset of symptoms could be late, and the clinical presentation initially may be mistaken for an injection-site reaction, which is a frequent known side effect of vaccines. These new cases do not prove causality between COVID-19 vaccination and HZ. Varicella-zoster virus remains latent in dorsal-root or ganglia after primary infection, and HZ caused by reactivation of varicella-zoster virus may occur spontaneously or be triggered. In our series, we did not observe medical history of immunosuppression, and no other known risk factors of HZ (eg, radiation therapy, physical trauma, fever after vaccination) were recorded. The pathophysiologic mechanism remains elusive, but local vaccine-induced immunomodulation or an inflammatory state may be involved.

Conclusion

Our case series highlights that clinicians must remain vigilant to diagnose HZ early to prevent potential complications, such as postherpetic neuralgia. Also, vaccination should not be contraindicated in patients with medical history of HZ; the occurrence of HZ does not justify avoiding the second injection of the vaccine due to the benefit of vaccination.

Since the end of 2019, COVID-19 infection caused by SARS-CoV-2 has spread in a worldwide pandemic. The first cutaneous manifestations possibly linked to COVID-19 were reported in spring 2020.¹ Herpes zoster (HZ) was suspected as a predictive cutaneous manifestation of COVID-19 with a debated prognostic significance.² The end of 2020 was marked with the beginning of vaccination against COVID-19, and safety studies reported few side effects after vaccination with nucleoside-modified messenger RNA (mRNA) COVID-19 vaccines.³ Real-life use of vaccines could lead to the occurrence of potential side effects (or fortuitous medical events) that were not observed in these studies. We report a series of 5 cases of HZ occurring after vaccination with a nucleoside-modified mRNA COVID-19 vaccine extracted from a declarative cohort of cutaneous reactions in our vaccination center.

Case Series

We identified 2 men and 3 women (Table) who experienced HZ after vaccination with a nucleoside-modified mRNA COVID-19 vaccine (Comirnaty, Pfizer-BioNTech). Patients fulfilled French governmental criteria for vaccination at the time of the report—older than 75 years or a health care professional—and they were vaccinated at the vaccination center of a French university hospital. The median age of the patients was 56 years (interquartile range [IQR], 51–82 years). One patient was diagnosed with COVID-19 in February 2020. A medical history of HZ was found in 1 patient. No medical history of immunosuppression was noted. Herpes zoster was observed on the same side of the body as the vaccination site in 4 patients. The median delay before the onset of symptoms was 6 days (IQR, 1–15 days) after injection. The median duration of the symptoms was 13 days (IQR, 11.5–16.5 days). Clinical signs of HZ were mild with few vesicles in 4 patients, and we observed a notably long delay between the onset of pain and the eruption of vesicles in 2 cases (4 and 10 days, respectively). The clinical diagnosis of HZ was confirmed by a dermatologist for all patients (Figures 1 and 2). Polymerase chain reaction assays for the detection of the varicella-zoster virus were performed in 2 cases and were positive. A complete blood cell count was performed in 1 patient, and we observed isolated lymphopenia (500/mm³ [reference range, 1000–4000/mm³]). Herpes zoster occurred after the first dose of vaccine in 4 patients and after the second dose for 1 patient. Three patients were treated with antiviral therapy (acyclovir) for 7 days. Three patients recovered from symptoms within 2 weeks and 2 patients within 1 week.

Comment

We report a series of HZ cases occurring after vaccination with a nucleoside-modified mRNA COVID-19 vaccine. We did not observe complicated HZ, and most of the time, HZ lesions were located on the same side of the body as the vaccine injection. One case of HZ after COVID-19 vaccination was reported by Bostan and Yalici-Armagan,⁴ but it followed injection with an inactivated vaccine, which is different from our series. Herpes zoster remains rarely reported, mainly following mRNA COVID-19 vaccination.⁵

Cases of HZ after vaccination have been reported after the live attenuated zoster or yellow fever vaccines, but HZ should not appear as a concomitant effect after any type of vaccines.^6,7 Kawai et al⁸ reported that the incidence rate of HZ ranged from 3 to 5 cases per 1000 person-years in North America, Europe, and Asia-Pacific. The risk for recurrence of HZ ranged from 1% to 6% depending on the type of study design, age distribution of studied populations, and definition.⁸ In another retrospective database analysis in Israel, the incidence density rate of HZ was 3.46 cases per 1000 person-years in the total population and 12.8 cases per 1000 person-years in immunocompromised patients, therefore the immunocompromised status is important to consider.⁹

In our declarative cohort of skin eruptions before vaccination, we recorded 11 cases of HZ among 148 skin eruptions (7.43%) at the time of the study, but the design of the study did not allow us to estimate the exact incidence of HZ in the global COVID-19–vaccinated population because our study was not based on a systematic and prospective analysis of all vaccinated patients. The comparison between the prevalence of HZ in the COVID-19–vaccinated population and the nonvaccinated population is difficult owing to the lack of data about HZ in the nonvaccinated population at the time of our analysis. Furthermore, we did not include all vaccinated patients in a prospective follow-up. We highlight the importance of medical history of patients that differed between vaccinated patients (at the time of our analysis) and the global population due to French governmental access criteria to vaccination. The link to prior SARS-CoV-2 infection was uncertain because a medical history of COVID-19 was found in only 1 patient. Only 1 patient had a history of HZ, which is not a contraindication of COVID-19 vaccination.

Postinjection pains are frequent with COVID-19 vaccines, but clinical signs such as extension of pain, burning sensation, and eruption of vesicles should lead the physician to consider the diagnosis of HZ, regardless of the delay between the injection and the symptoms. Indeed, the onset of symptoms could be late, and the clinical presentation initially may be mistaken for an injection-site reaction, which is a frequent known side effect of vaccines. These new cases do not prove causality between COVID-19 vaccination and HZ. Varicella-zoster virus remains latent in dorsal-root or ganglia after primary infection, and HZ caused by reactivation of varicella-zoster virus may occur spontaneously or be triggered. In our series, we did not observe medical history of immunosuppression, and no other known risk factors of HZ (eg, radiation therapy, physical trauma, fever after vaccination) were recorded. The pathophysiologic mechanism remains elusive, but local vaccine-induced immunomodulation or an inflammatory state may be involved.

Conclusion

Our case series highlights that clinicians must remain vigilant to diagnose HZ early to prevent potential complications, such as postherpetic neuralgia. Also, vaccination should not be contraindicated in patients with medical history of HZ; the occurrence of HZ does not justify avoiding the second injection of the vaccine due to the benefit of vaccination.

Since the end of 2019, COVID-19 infection caused by SARS-CoV-2 has spread in a worldwide pandemic. The first cutaneous manifestations possibly linked to COVID-19 were reported in spring 2020.¹ Herpes zoster (HZ) was suspected as a predictive cutaneous manifestation of COVID-19 with a debated prognostic significance.² The end of 2020 was marked with the beginning of vaccination against COVID-19, and safety studies reported few side effects after vaccination with nucleoside-modified messenger RNA (mRNA) COVID-19 vaccines.³ Real-life use of vaccines could lead to the occurrence of potential side effects (or fortuitous medical events) that were not observed in these studies. We report a series of 5 cases of HZ occurring after vaccination with a nucleoside-modified mRNA COVID-19 vaccine extracted from a declarative cohort of cutaneous reactions in our vaccination center.

Case Series

We identified 2 men and 3 women (Table) who experienced HZ after vaccination with a nucleoside-modified mRNA COVID-19 vaccine (Comirnaty, Pfizer-BioNTech). Patients fulfilled French governmental criteria for vaccination at the time of the report—older than 75 years or a health care professional—and they were vaccinated at the vaccination center of a French university hospital. The median age of the patients was 56 years (interquartile range [IQR], 51–82 years). One patient was diagnosed with COVID-19 in February 2020. A medical history of HZ was found in 1 patient. No medical history of immunosuppression was noted. Herpes zoster was observed on the same side of the body as the vaccination site in 4 patients. The median delay before the onset of symptoms was 6 days (IQR, 1–15 days) after injection. The median duration of the symptoms was 13 days (IQR, 11.5–16.5 days). Clinical signs of HZ were mild with few vesicles in 4 patients, and we observed a notably long delay between the onset of pain and the eruption of vesicles in 2 cases (4 and 10 days, respectively). The clinical diagnosis of HZ was confirmed by a dermatologist for all patients (Figures 1 and 2). Polymerase chain reaction assays for the detection of the varicella-zoster virus were performed in 2 cases and were positive. A complete blood cell count was performed in 1 patient, and we observed isolated lymphopenia (500/mm³ [reference range, 1000–4000/mm³]). Herpes zoster occurred after the first dose of vaccine in 4 patients and after the second dose for 1 patient. Three patients were treated with antiviral therapy (acyclovir) for 7 days. Three patients recovered from symptoms within 2 weeks and 2 patients within 1 week.

Comment

We report a series of HZ cases occurring after vaccination with a nucleoside-modified mRNA COVID-19 vaccine. We did not observe complicated HZ, and most of the time, HZ lesions were located on the same side of the body as the vaccine injection. One case of HZ after COVID-19 vaccination was reported by Bostan and Yalici-Armagan,⁴ but it followed injection with an inactivated vaccine, which is different from our series. Herpes zoster remains rarely reported, mainly following mRNA COVID-19 vaccination.⁵

Cases of HZ after vaccination have been reported after the live attenuated zoster or yellow fever vaccines, but HZ should not appear as a concomitant effect after any type of vaccines.^6,7 Kawai et al⁸ reported that the incidence rate of HZ ranged from 3 to 5 cases per 1000 person-years in North America, Europe, and Asia-Pacific. The risk for recurrence of HZ ranged from 1% to 6% depending on the type of study design, age distribution of studied populations, and definition.⁸ In another retrospective database analysis in Israel, the incidence density rate of HZ was 3.46 cases per 1000 person-years in the total population and 12.8 cases per 1000 person-years in immunocompromised patients, therefore the immunocompromised status is important to consider.⁹

In our declarative cohort of skin eruptions before vaccination, we recorded 11 cases of HZ among 148 skin eruptions (7.43%) at the time of the study, but the design of the study did not allow us to estimate the exact incidence of HZ in the global COVID-19–vaccinated population because our study was not based on a systematic and prospective analysis of all vaccinated patients. The comparison between the prevalence of HZ in the COVID-19–vaccinated population and the nonvaccinated population is difficult owing to the lack of data about HZ in the nonvaccinated population at the time of our analysis. Furthermore, we did not include all vaccinated patients in a prospective follow-up. We highlight the importance of medical history of patients that differed between vaccinated patients (at the time of our analysis) and the global population due to French governmental access criteria to vaccination. The link to prior SARS-CoV-2 infection was uncertain because a medical history of COVID-19 was found in only 1 patient. Only 1 patient had a history of HZ, which is not a contraindication of COVID-19 vaccination.

Postinjection pains are frequent with COVID-19 vaccines, but clinical signs such as extension of pain, burning sensation, and eruption of vesicles should lead the physician to consider the diagnosis of HZ, regardless of the delay between the injection and the symptoms. Indeed, the onset of symptoms could be late, and the clinical presentation initially may be mistaken for an injection-site reaction, which is a frequent known side effect of vaccines. These new cases do not prove causality between COVID-19 vaccination and HZ. Varicella-zoster virus remains latent in dorsal-root or ganglia after primary infection, and HZ caused by reactivation of varicella-zoster virus may occur spontaneously or be triggered. In our series, we did not observe medical history of immunosuppression, and no other known risk factors of HZ (eg, radiation therapy, physical trauma, fever after vaccination) were recorded. The pathophysiologic mechanism remains elusive, but local vaccine-induced immunomodulation or an inflammatory state may be involved.

Conclusion

Our case series highlights that clinicians must remain vigilant to diagnose HZ early to prevent potential complications, such as postherpetic neuralgia. Also, vaccination should not be contraindicated in patients with medical history of HZ; the occurrence of HZ does not justify avoiding the second injection of the vaccine due to the benefit of vaccination.

The CDC has released two studies that showed vaccine safety for ages 5-11 and emphasized the importance of vaccinating children against the coronavirus to prevent serious illness and hospitalization.

In one study published in the Morbidity and Mortality Weekly Report, researchers found that serious problems were rare among children who had received the Pfizer vaccine.

In another study, researchers looked at hundreds of pediatric hospitalizations from the summer and found that nearly all of children who developed severe COVID-19 weren’t fully vaccinated.

“This study demonstrates that unvaccinated children hospitalized for COVID-19 could experience severe disease and reinforces the importance of vaccination of all eligible children to provide individual protection and to protect those who are not yet eligible to be vaccinated,” the authors of the second study wrote.

Nearly 9 million doses of the Pfizer vaccine have been given to children aged 5-11 in the United States so far, according to The New York Times. By mid-December, or about 6 weeks after the age group became eligible for vaccination in October, the CDC said it had received very few reports of serious problems.

CDC researchers evaluated reports received from doctors and the public, including survey responses from parents and guardians of about 43,000 children between ages 5 and 11. Many children reported nonserious events such as pain at the injection site, fatigue, or a headache, especially after the second dose.

Among more than 4,100 adverse event reports received in November and December, 100 were for serious events, with the most common being fever or vomiting.

The CDC had received 11 verified reports of myocarditis, or inflammation of the heart muscle, which has been noted as a rare side effect of the vaccine among boys and men between ages 12 and 29. Among those, seven children had already recovered and four were still recovering at the time of the report.

The CDC received reports of two deaths – girls who were aged 5 and 6 – who had chronic medical conditions and were in “fragile health” before their shots. The agency said that no data suggested a “causal association between death and vaccination.”

The CDC also received some reports that children between ages 5 and 11 received the larger vaccine dose meant for older children and adults. Most reports said that the children didn’t experience any problems after an incorrect dose.

In a separate study about pediatric hospitalizations, CDC researchers looked at more than 700 children under age 18 who were hospitalized for COVID-19 in July and August at six children’s hospitals in Arkansas, Florida, Illinois, Louisiana, Texas, and Washington, D.C.

Researchers found that only one of the 272 vaccine-eligible patients between ages 12 and 17 had been fully vaccinated, and 12 were partially vaccinated.

In addition, about two-thirds of the hospitalized children between ages 12 and 17 had an underlying condition, with obesity being the most common. About one-third of children under age 5 had more than one viral infection.

Overall, about 30% of the children had to be treated in intensive care units, and 15% needed invasive medical ventilation, CDC researchers found. Nearly 3% had multisystem inflammatory syndrome in children, or MIS-C, which is a rare but serious inflammatory condition associated with COVID-19.

Among all the children hospitalized with COVID-19, about 1.5% died.

“Few vaccine-eligible patients hospitalized for COVID-19 were vaccinated, highlighting the importance of vaccination for those aged ≥5 years and other prevention strategies to protect children and adolescents from COVID-19, particularly those with underlying medical conditions,” study authors wrote.

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

The CDC has released two studies that showed vaccine safety for ages 5-11 and emphasized the importance of vaccinating children against the coronavirus to prevent serious illness and hospitalization.

In one study published in the Morbidity and Mortality Weekly Report, researchers found that serious problems were rare among children who had received the Pfizer vaccine.

In another study, researchers looked at hundreds of pediatric hospitalizations from the summer and found that nearly all of children who developed severe COVID-19 weren’t fully vaccinated.

“This study demonstrates that unvaccinated children hospitalized for COVID-19 could experience severe disease and reinforces the importance of vaccination of all eligible children to provide individual protection and to protect those who are not yet eligible to be vaccinated,” the authors of the second study wrote.

Nearly 9 million doses of the Pfizer vaccine have been given to children aged 5-11 in the United States so far, according to The New York Times. By mid-December, or about 6 weeks after the age group became eligible for vaccination in October, the CDC said it had received very few reports of serious problems.

CDC researchers evaluated reports received from doctors and the public, including survey responses from parents and guardians of about 43,000 children between ages 5 and 11. Many children reported nonserious events such as pain at the injection site, fatigue, or a headache, especially after the second dose.

Among more than 4,100 adverse event reports received in November and December, 100 were for serious events, with the most common being fever or vomiting.

The CDC had received 11 verified reports of myocarditis, or inflammation of the heart muscle, which has been noted as a rare side effect of the vaccine among boys and men between ages 12 and 29. Among those, seven children had already recovered and four were still recovering at the time of the report.

The CDC received reports of two deaths – girls who were aged 5 and 6 – who had chronic medical conditions and were in “fragile health” before their shots. The agency said that no data suggested a “causal association between death and vaccination.”

The CDC also received some reports that children between ages 5 and 11 received the larger vaccine dose meant for older children and adults. Most reports said that the children didn’t experience any problems after an incorrect dose.

In a separate study about pediatric hospitalizations, CDC researchers looked at more than 700 children under age 18 who were hospitalized for COVID-19 in July and August at six children’s hospitals in Arkansas, Florida, Illinois, Louisiana, Texas, and Washington, D.C.

Researchers found that only one of the 272 vaccine-eligible patients between ages 12 and 17 had been fully vaccinated, and 12 were partially vaccinated.

In addition, about two-thirds of the hospitalized children between ages 12 and 17 had an underlying condition, with obesity being the most common. About one-third of children under age 5 had more than one viral infection.

Overall, about 30% of the children had to be treated in intensive care units, and 15% needed invasive medical ventilation, CDC researchers found. Nearly 3% had multisystem inflammatory syndrome in children, or MIS-C, which is a rare but serious inflammatory condition associated with COVID-19.

Among all the children hospitalized with COVID-19, about 1.5% died.

“Few vaccine-eligible patients hospitalized for COVID-19 were vaccinated, highlighting the importance of vaccination for those aged ≥5 years and other prevention strategies to protect children and adolescents from COVID-19, particularly those with underlying medical conditions,” study authors wrote.

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

The CDC has released two studies that showed vaccine safety for ages 5-11 and emphasized the importance of vaccinating children against the coronavirus to prevent serious illness and hospitalization.

In one study published in the Morbidity and Mortality Weekly Report, researchers found that serious problems were rare among children who had received the Pfizer vaccine.

In another study, researchers looked at hundreds of pediatric hospitalizations from the summer and found that nearly all of children who developed severe COVID-19 weren’t fully vaccinated.

“This study demonstrates that unvaccinated children hospitalized for COVID-19 could experience severe disease and reinforces the importance of vaccination of all eligible children to provide individual protection and to protect those who are not yet eligible to be vaccinated,” the authors of the second study wrote.

Nearly 9 million doses of the Pfizer vaccine have been given to children aged 5-11 in the United States so far, according to The New York Times. By mid-December, or about 6 weeks after the age group became eligible for vaccination in October, the CDC said it had received very few reports of serious problems.

CDC researchers evaluated reports received from doctors and the public, including survey responses from parents and guardians of about 43,000 children between ages 5 and 11. Many children reported nonserious events such as pain at the injection site, fatigue, or a headache, especially after the second dose.

Among more than 4,100 adverse event reports received in November and December, 100 were for serious events, with the most common being fever or vomiting.

The CDC had received 11 verified reports of myocarditis, or inflammation of the heart muscle, which has been noted as a rare side effect of the vaccine among boys and men between ages 12 and 29. Among those, seven children had already recovered and four were still recovering at the time of the report.

The CDC received reports of two deaths – girls who were aged 5 and 6 – who had chronic medical conditions and were in “fragile health” before their shots. The agency said that no data suggested a “causal association between death and vaccination.”

The CDC also received some reports that children between ages 5 and 11 received the larger vaccine dose meant for older children and adults. Most reports said that the children didn’t experience any problems after an incorrect dose.

In a separate study about pediatric hospitalizations, CDC researchers looked at more than 700 children under age 18 who were hospitalized for COVID-19 in July and August at six children’s hospitals in Arkansas, Florida, Illinois, Louisiana, Texas, and Washington, D.C.

Researchers found that only one of the 272 vaccine-eligible patients between ages 12 and 17 had been fully vaccinated, and 12 were partially vaccinated.

In addition, about two-thirds of the hospitalized children between ages 12 and 17 had an underlying condition, with obesity being the most common. About one-third of children under age 5 had more than one viral infection.

Overall, about 30% of the children had to be treated in intensive care units, and 15% needed invasive medical ventilation, CDC researchers found. Nearly 3% had multisystem inflammatory syndrome in children, or MIS-C, which is a rare but serious inflammatory condition associated with COVID-19.

Among all the children hospitalized with COVID-19, about 1.5% died.

“Few vaccine-eligible patients hospitalized for COVID-19 were vaccinated, highlighting the importance of vaccination for those aged ≥5 years and other prevention strategies to protect children and adolescents from COVID-19, particularly those with underlying medical conditions,” study authors wrote.

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

The pandemic has created a hostile environment for pregnant people and their babies.

Stress levels among expectant mothers have soared. Pregnant women with COVID are 5 times as likely as uninfected pregnant people to require intensive care and 22 times as likely to die. Infected moms are four times as likely to have a stillborn child.

Yet some of the pandemic’s greatest threats to infants’ health may not be apparent for years or even decades.

That’s because babies of COVID-infected moms are 60% more likely to be born very prematurely, which increases the danger of infant mortality and long-term disabilities such as cerebral palsy, asthma, and hearing loss, as well as a child’s risk of adult disease, including depression, anxiety, heart disease, and kidney disease.

Studies have linked fever and infection during pregnancy to developmental and psychiatric conditions such as autism, depression, and schizophrenia.

“Some of these conditions do not show up until middle childhood or early adult life, but they have their origins in fetal life,” said Evdokia Anagnostou, MD, a child neurologist at Holland Bloorview Kids Rehabilitation Hospital and a pediatrics professor at the University of Toronto.

For fetuses exposed to COVID, the greatest danger is usually not the coronavirus itself, but the mother’s immune system.

Both severe COVID infections and the strain of the pandemic can expose fetuses to harmful inflammation, which can occur when a mother’s immune system is fighting a virus or when stress hormones send nonstop alarm signals.

Prenatal inflammation “changes the way the brain develops and, depending on the timing of the infection, it can change the way the heart or kidneys develop,” Dr. Anagnostou said.

Although health officials have strongly recommended COVID vaccines for pregnant people, only 35% are fully vaccinated.

At least 150,000 pregnant women have been diagnosed with COVID; more than 25,000 of them have been hospitalized, and 249 have died, according to the Centers for Disease Control and Prevention.

Although most babies will be fine, even a small increase in the percentage of children with special medical or educational needs could have a large effect on the population, given the huge number of COVID infections, Dr. Anagnostou said.

“If someone has a baby who is doing well, that is what they should focus on,” Dr. Anagnostou said. “But from a public health point of view, we need to follow women who experienced severe COVID and their babies to understand the impact.”

Learning from history

Researchers in the United States and other countries are already studying “the COVID generation” to see whether these children have more health issues than those conceived or born before 2020.

Previous crises have shown that the challenges fetuses face in the womb – such as maternal infections, hunger, stress, and hormone-disrupting chemicals – can leave a lasting imprint on their health, as well as that of their children and grandchildren, said Frederick Kaskel, MD, director of pediatric nephrology at the Children’s Hospital at Montefiore, New York.

People whose mothers were pregnant during surges in the 1918 influenza pandemic, for example, had poorer health throughout their lives, compared with Americans born at other times, said John McCarthy, who is a medical student at Albert Einstein College of Medicine, New York, and cowrote a recent review in JAMA Pediatrics with Dr. Kaskel.

Researchers don’t know exactly which moms were infected with pandemic flu, Mr. McCarthy said. But women who were pregnant during major surges – when infection was widespread – had children with higher rates of heart disease or diabetes. These children were also less successful in school, less economically productive, and more likely to live with a disability.

Because organ systems develop during different periods of pregnancy, fetuses exposed during the first trimester may face different risks than those exposed toward the end of pregnancy, Mr. McCarthy said. For example, people born in the fall of 1918 were 50% more likely than others to develop kidney disease; that may reflect an exposure to the pandemic in the third trimester, while the kidneys were still developing.

Nearly 2 years into the COVID pandemic, researchers have begun to publish preliminary observations of infants exposed to COVID infections and stress before birth.

Although Dr. Anagnostou noted that it’s too early to reach definitive conclusions, “there is evidence that babies born to moms with severe COVID infections have changes to their immune system,” she said. “It’s enough to make us worry a little bit.”

Damaging a fetal security system

The good news about the coronavirus is that it seldom crosses the placenta, the organ tasked with protecting a developing fetus from infections and providing it with oxygen. So moms with COVID rarely give the virus to their children before birth.

That’s important, because some viruses that directly infect the fetus – such as Zika – can cause devastating birth defects, said Karin Nielsen-Saines, MD, a specialist in pediatric infectious diseases at University of California, Los Angeles.

But studies also suggest that inflammation from a mother’s COVID infection can injure the placenta, said Jeffery Goldstein, MD, an assistant professor of pathology at Northwestern University, Chicago. In a study published in American Journal of Clinical Pathology , Dr. Goldstein and his coauthors found that placentas from COVID-infected moms had more abnormal blood vessels than placentas from patients without COVID, making it harder for them to deliver sufficient oxygen to the fetus.

Placental damage can also lead to preeclampsia, a serious complication of pregnancy that can cause a mother’s blood pressure to spike.

Preeclampsia occurs when blood vessels in the placenta don’t develop or function properly, forcing the mother’s heart to work harder to get blood to the fetus, which may not receive enough oxygen and nutrients. Preeclampsia also predisposes women to heart attacks and strokes later in life.

Rewiring the immune system

In some cases, COVID also appears to rewire a baby’s immune response, Dr. Nielsen-Saines said.

In an October study in the journal Cell Reports Medicine, Dr. Nielsen-Saines and her coauthors found that infants born to people with severe COVID infections had a different mix of immune cells and proteins than other babies. None of the newborns tested positive for the coronavirus.

The immune changes are concerning, Dr. Nielsen-Saines said, because this pattern of immune cells and proteins has previously been found in infants with respiratory problems and in some cases poor neurodevelopment.

Notably, all the babies in her study appear healthy, said Dr. Nielsen-Saines, who plans to follow them for 3 years to see whether these early signals translate into developmental delays, such as problems talking, walking, or interacting with others.

“How big of a difference does any of this make in the baby?” asked Dr. Anagnostou. “We won’t know for a few years. All we can do is try to be as prepared as possible.”

Increasing the risk for boys

Boys could face higher risks from COVID, even before birth.

Males are generally more vulnerable than females as fetuses and newborns; they’re more likely to be born prematurely and to die as infants. Preterm boys also have a higher risk of disability and death.

But coronavirus infection poses special dangers, said Sabra Klein, PhD, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, Baltimore.

That’s because boys are disproportionately affected by conditions linked to maternal infections. Boys are four times as likely as girls to be diagnosed with autism or attention-deficit/hyperactivity disorder, for example, while men are 75% more likely than women to develop schizophrenia.

Scientists don’t fully understand why boys appear more fragile in the womb, although testosterone – which can dampen immune response – may play a role, said Kristina Adams Waldorf, MD, a professor of obstetrics and gynecology at the University of Washington.

Men generally mount weaker immune responses than women and more often develop severe COVID infections. Recent research suggests boys with COVID are more likely than girls to become seriously ill or develop a rare inflammatory condition called multisystem inflammatory syndrome.

New research on COVID could help illuminate this vulnerability.

In a study published in October, researchers found that the sex of a fetus influences the way its placenta responds to COVID, as well as how its mother’s immune system responds.

Pregnant people infected with COVID made fewer antibodies against the coronavirus if they were carrying male fetuses than if they were carrying females. Mothers also transferred fewer antibodies to boys than to girls, said Andrea Edlow, MD, senior author of the study and a maternal-fetal medicine specialist at Massachusetts General Hospital, Boston.

When examining the placentas of male fetuses after delivery, researchers found changes that could leave boys less protected against damaging inflammation.

The sex of a fetus can influence its mother’s response to other illnesses, as well.

For example, research shows that pregnant women with asthma have worse symptoms if they’re carrying a female. Women carrying males are slightly more likely to develop gestational diabetes.

Dr. Edlow said her findings raise questions about the “cross talk” between mother and baby. “The mom’s immune system is sensing there is a male fetus,” Dr. Edlow said. “And the fetus is actively communicating with the mom’s immune system.”

Boosting toxic stress

Rates of depression and stress among pregnant women have increased dramatically during the pandemic.

That’s concerning because chronic stress can lead to inflammation, affecting the babies of both infected and uninfected women, Dr. Anagnostou said.

Studies consistently show that infants born to mothers who experience significant stress during pregnancy have higher rates of short- and long-term health damage – including heart defects and obesity – than babies born to women with less stress.

“We know that inflammation directly influences the way a baby’s brain develops,” said Elinor Sullivan, PhD, an associate professor in psychiatry at Oregon Health & Science University, Portland.

Lockdowns, travel restrictions and physical distancing left many pregnant women without the support of family and friends. The stress of losing a loved one, a job, or a home further heightens the risks to moms and babies, said Dr. Sullivan, who is following children born during the pandemic for 5 years.

In research that has not yet been published, Dr. Sullivan found that babies of women who were pregnant during the pandemic showed more sadness and negative emotions in the first year of life, compared with infants of women who were pregnant before the pandemic.

The findings show the importance of helping and protecting pregnant people before and after delivery, said Dr. Sullivan, who conducted a separate study that found women who received more social support were less depressed.

Italian researchers are also studying the effect of maternal stress on infants’ behavior, as well as the way their genes are regulated.

Although stress-related inflammation doesn’t alter the structure of a baby’s genes, it can influence whether they’re turned on and off, said Livio Provenzi, PhD, a psychologist at the C. Mondino National Institute of Neurology Foundation in Pavia, Italy.

In Dr. Provenzi’s study of 163 mother-baby pairs he found differences in how genes that regulate the stress response were activated. Genes that help people respond to stress were more likely to be turned off in babies whose moms reported the most stress during pregnancy. The same moms also reported that their babies cried more and were fussier when they were 3 months old.

Researchers usually prefer to make in-person observations of babies as they interact with their mothers, Dr. Provenzi said. But because of the pandemic, Dr. Provenzi asked mothers to fill out questionnaires about infant behavior. He plans to observe mothers and babies in person when the children are 12 months old.

While vaccinating pregnant people is the best way to protect them and their fetuses from the virus, Dr. Anagnostou said, society needs to do more to preserve expectant mothers’ mental health.

“We can’t escape the fact that we’ve lived through 2 years of a pandemic,” Dr. Anagnostou said. “But we can think about opportunities for reducing the risk.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The pandemic has created a hostile environment for pregnant people and their babies.

Stress levels among expectant mothers have soared. Pregnant women with COVID are 5 times as likely as uninfected pregnant people to require intensive care and 22 times as likely to die. Infected moms are four times as likely to have a stillborn child.

Yet some of the pandemic’s greatest threats to infants’ health may not be apparent for years or even decades.

That’s because babies of COVID-infected moms are 60% more likely to be born very prematurely, which increases the danger of infant mortality and long-term disabilities such as cerebral palsy, asthma, and hearing loss, as well as a child’s risk of adult disease, including depression, anxiety, heart disease, and kidney disease.

Studies have linked fever and infection during pregnancy to developmental and psychiatric conditions such as autism, depression, and schizophrenia.

“Some of these conditions do not show up until middle childhood or early adult life, but they have their origins in fetal life,” said Evdokia Anagnostou, MD, a child neurologist at Holland Bloorview Kids Rehabilitation Hospital and a pediatrics professor at the University of Toronto.

For fetuses exposed to COVID, the greatest danger is usually not the coronavirus itself, but the mother’s immune system.

Both severe COVID infections and the strain of the pandemic can expose fetuses to harmful inflammation, which can occur when a mother’s immune system is fighting a virus or when stress hormones send nonstop alarm signals.

Prenatal inflammation “changes the way the brain develops and, depending on the timing of the infection, it can change the way the heart or kidneys develop,” Dr. Anagnostou said.

Although health officials have strongly recommended COVID vaccines for pregnant people, only 35% are fully vaccinated.

At least 150,000 pregnant women have been diagnosed with COVID; more than 25,000 of them have been hospitalized, and 249 have died, according to the Centers for Disease Control and Prevention.

Although most babies will be fine, even a small increase in the percentage of children with special medical or educational needs could have a large effect on the population, given the huge number of COVID infections, Dr. Anagnostou said.

“If someone has a baby who is doing well, that is what they should focus on,” Dr. Anagnostou said. “But from a public health point of view, we need to follow women who experienced severe COVID and their babies to understand the impact.”

Learning from history

Researchers in the United States and other countries are already studying “the COVID generation” to see whether these children have more health issues than those conceived or born before 2020.

Previous crises have shown that the challenges fetuses face in the womb – such as maternal infections, hunger, stress, and hormone-disrupting chemicals – can leave a lasting imprint on their health, as well as that of their children and grandchildren, said Frederick Kaskel, MD, director of pediatric nephrology at the Children’s Hospital at Montefiore, New York.

People whose mothers were pregnant during surges in the 1918 influenza pandemic, for example, had poorer health throughout their lives, compared with Americans born at other times, said John McCarthy, who is a medical student at Albert Einstein College of Medicine, New York, and cowrote a recent review in JAMA Pediatrics with Dr. Kaskel.

Researchers don’t know exactly which moms were infected with pandemic flu, Mr. McCarthy said. But women who were pregnant during major surges – when infection was widespread – had children with higher rates of heart disease or diabetes. These children were also less successful in school, less economically productive, and more likely to live with a disability.

Because organ systems develop during different periods of pregnancy, fetuses exposed during the first trimester may face different risks than those exposed toward the end of pregnancy, Mr. McCarthy said. For example, people born in the fall of 1918 were 50% more likely than others to develop kidney disease; that may reflect an exposure to the pandemic in the third trimester, while the kidneys were still developing.

Nearly 2 years into the COVID pandemic, researchers have begun to publish preliminary observations of infants exposed to COVID infections and stress before birth.

Although Dr. Anagnostou noted that it’s too early to reach definitive conclusions, “there is evidence that babies born to moms with severe COVID infections have changes to their immune system,” she said. “It’s enough to make us worry a little bit.”

Damaging a fetal security system

The good news about the coronavirus is that it seldom crosses the placenta, the organ tasked with protecting a developing fetus from infections and providing it with oxygen. So moms with COVID rarely give the virus to their children before birth.

That’s important, because some viruses that directly infect the fetus – such as Zika – can cause devastating birth defects, said Karin Nielsen-Saines, MD, a specialist in pediatric infectious diseases at University of California, Los Angeles.

But studies also suggest that inflammation from a mother’s COVID infection can injure the placenta, said Jeffery Goldstein, MD, an assistant professor of pathology at Northwestern University, Chicago. In a study published in American Journal of Clinical Pathology , Dr. Goldstein and his coauthors found that placentas from COVID-infected moms had more abnormal blood vessels than placentas from patients without COVID, making it harder for them to deliver sufficient oxygen to the fetus.

Placental damage can also lead to preeclampsia, a serious complication of pregnancy that can cause a mother’s blood pressure to spike.

Preeclampsia occurs when blood vessels in the placenta don’t develop or function properly, forcing the mother’s heart to work harder to get blood to the fetus, which may not receive enough oxygen and nutrients. Preeclampsia also predisposes women to heart attacks and strokes later in life.

Rewiring the immune system

In some cases, COVID also appears to rewire a baby’s immune response, Dr. Nielsen-Saines said.

In an October study in the journal Cell Reports Medicine, Dr. Nielsen-Saines and her coauthors found that infants born to people with severe COVID infections had a different mix of immune cells and proteins than other babies. None of the newborns tested positive for the coronavirus.

The immune changes are concerning, Dr. Nielsen-Saines said, because this pattern of immune cells and proteins has previously been found in infants with respiratory problems and in some cases poor neurodevelopment.

Notably, all the babies in her study appear healthy, said Dr. Nielsen-Saines, who plans to follow them for 3 years to see whether these early signals translate into developmental delays, such as problems talking, walking, or interacting with others.

“How big of a difference does any of this make in the baby?” asked Dr. Anagnostou. “We won’t know for a few years. All we can do is try to be as prepared as possible.”

Increasing the risk for boys

Boys could face higher risks from COVID, even before birth.

Males are generally more vulnerable than females as fetuses and newborns; they’re more likely to be born prematurely and to die as infants. Preterm boys also have a higher risk of disability and death.

But coronavirus infection poses special dangers, said Sabra Klein, PhD, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, Baltimore.

That’s because boys are disproportionately affected by conditions linked to maternal infections. Boys are four times as likely as girls to be diagnosed with autism or attention-deficit/hyperactivity disorder, for example, while men are 75% more likely than women to develop schizophrenia.

Scientists don’t fully understand why boys appear more fragile in the womb, although testosterone – which can dampen immune response – may play a role, said Kristina Adams Waldorf, MD, a professor of obstetrics and gynecology at the University of Washington.

Men generally mount weaker immune responses than women and more often develop severe COVID infections. Recent research suggests boys with COVID are more likely than girls to become seriously ill or develop a rare inflammatory condition called multisystem inflammatory syndrome.

New research on COVID could help illuminate this vulnerability.

In a study published in October, researchers found that the sex of a fetus influences the way its placenta responds to COVID, as well as how its mother’s immune system responds.

Pregnant people infected with COVID made fewer antibodies against the coronavirus if they were carrying male fetuses than if they were carrying females. Mothers also transferred fewer antibodies to boys than to girls, said Andrea Edlow, MD, senior author of the study and a maternal-fetal medicine specialist at Massachusetts General Hospital, Boston.

When examining the placentas of male fetuses after delivery, researchers found changes that could leave boys less protected against damaging inflammation.

The sex of a fetus can influence its mother’s response to other illnesses, as well.

For example, research shows that pregnant women with asthma have worse symptoms if they’re carrying a female. Women carrying males are slightly more likely to develop gestational diabetes.

Dr. Edlow said her findings raise questions about the “cross talk” between mother and baby. “The mom’s immune system is sensing there is a male fetus,” Dr. Edlow said. “And the fetus is actively communicating with the mom’s immune system.”

Boosting toxic stress

Rates of depression and stress among pregnant women have increased dramatically during the pandemic.

That’s concerning because chronic stress can lead to inflammation, affecting the babies of both infected and uninfected women, Dr. Anagnostou said.

Studies consistently show that infants born to mothers who experience significant stress during pregnancy have higher rates of short- and long-term health damage – including heart defects and obesity – than babies born to women with less stress.

“We know that inflammation directly influences the way a baby’s brain develops,” said Elinor Sullivan, PhD, an associate professor in psychiatry at Oregon Health & Science University, Portland.

Lockdowns, travel restrictions and physical distancing left many pregnant women without the support of family and friends. The stress of losing a loved one, a job, or a home further heightens the risks to moms and babies, said Dr. Sullivan, who is following children born during the pandemic for 5 years.

In research that has not yet been published, Dr. Sullivan found that babies of women who were pregnant during the pandemic showed more sadness and negative emotions in the first year of life, compared with infants of women who were pregnant before the pandemic.

The findings show the importance of helping and protecting pregnant people before and after delivery, said Dr. Sullivan, who conducted a separate study that found women who received more social support were less depressed.

Italian researchers are also studying the effect of maternal stress on infants’ behavior, as well as the way their genes are regulated.

Although stress-related inflammation doesn’t alter the structure of a baby’s genes, it can influence whether they’re turned on and off, said Livio Provenzi, PhD, a psychologist at the C. Mondino National Institute of Neurology Foundation in Pavia, Italy.

In Dr. Provenzi’s study of 163 mother-baby pairs he found differences in how genes that regulate the stress response were activated. Genes that help people respond to stress were more likely to be turned off in babies whose moms reported the most stress during pregnancy. The same moms also reported that their babies cried more and were fussier when they were 3 months old.

Researchers usually prefer to make in-person observations of babies as they interact with their mothers, Dr. Provenzi said. But because of the pandemic, Dr. Provenzi asked mothers to fill out questionnaires about infant behavior. He plans to observe mothers and babies in person when the children are 12 months old.

While vaccinating pregnant people is the best way to protect them and their fetuses from the virus, Dr. Anagnostou said, society needs to do more to preserve expectant mothers’ mental health.

“We can’t escape the fact that we’ve lived through 2 years of a pandemic,” Dr. Anagnostou said. “But we can think about opportunities for reducing the risk.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The pandemic has created a hostile environment for pregnant people and their babies.

Stress levels among expectant mothers have soared. Pregnant women with COVID are 5 times as likely as uninfected pregnant people to require intensive care and 22 times as likely to die. Infected moms are four times as likely to have a stillborn child.

Yet some of the pandemic’s greatest threats to infants’ health may not be apparent for years or even decades.

That’s because babies of COVID-infected moms are 60% more likely to be born very prematurely, which increases the danger of infant mortality and long-term disabilities such as cerebral palsy, asthma, and hearing loss, as well as a child’s risk of adult disease, including depression, anxiety, heart disease, and kidney disease.

Studies have linked fever and infection during pregnancy to developmental and psychiatric conditions such as autism, depression, and schizophrenia.

“Some of these conditions do not show up until middle childhood or early adult life, but they have their origins in fetal life,” said Evdokia Anagnostou, MD, a child neurologist at Holland Bloorview Kids Rehabilitation Hospital and a pediatrics professor at the University of Toronto.

For fetuses exposed to COVID, the greatest danger is usually not the coronavirus itself, but the mother’s immune system.

Both severe COVID infections and the strain of the pandemic can expose fetuses to harmful inflammation, which can occur when a mother’s immune system is fighting a virus or when stress hormones send nonstop alarm signals.

Prenatal inflammation “changes the way the brain develops and, depending on the timing of the infection, it can change the way the heart or kidneys develop,” Dr. Anagnostou said.

Although health officials have strongly recommended COVID vaccines for pregnant people, only 35% are fully vaccinated.

At least 150,000 pregnant women have been diagnosed with COVID; more than 25,000 of them have been hospitalized, and 249 have died, according to the Centers for Disease Control and Prevention.

Although most babies will be fine, even a small increase in the percentage of children with special medical or educational needs could have a large effect on the population, given the huge number of COVID infections, Dr. Anagnostou said.

“If someone has a baby who is doing well, that is what they should focus on,” Dr. Anagnostou said. “But from a public health point of view, we need to follow women who experienced severe COVID and their babies to understand the impact.”

Learning from history

Researchers in the United States and other countries are already studying “the COVID generation” to see whether these children have more health issues than those conceived or born before 2020.

Previous crises have shown that the challenges fetuses face in the womb – such as maternal infections, hunger, stress, and hormone-disrupting chemicals – can leave a lasting imprint on their health, as well as that of their children and grandchildren, said Frederick Kaskel, MD, director of pediatric nephrology at the Children’s Hospital at Montefiore, New York.

People whose mothers were pregnant during surges in the 1918 influenza pandemic, for example, had poorer health throughout their lives, compared with Americans born at other times, said John McCarthy, who is a medical student at Albert Einstein College of Medicine, New York, and cowrote a recent review in JAMA Pediatrics with Dr. Kaskel.

Researchers don’t know exactly which moms were infected with pandemic flu, Mr. McCarthy said. But women who were pregnant during major surges – when infection was widespread – had children with higher rates of heart disease or diabetes. These children were also less successful in school, less economically productive, and more likely to live with a disability.

Because organ systems develop during different periods of pregnancy, fetuses exposed during the first trimester may face different risks than those exposed toward the end of pregnancy, Mr. McCarthy said. For example, people born in the fall of 1918 were 50% more likely than others to develop kidney disease; that may reflect an exposure to the pandemic in the third trimester, while the kidneys were still developing.

Nearly 2 years into the COVID pandemic, researchers have begun to publish preliminary observations of infants exposed to COVID infections and stress before birth.

Although Dr. Anagnostou noted that it’s too early to reach definitive conclusions, “there is evidence that babies born to moms with severe COVID infections have changes to their immune system,” she said. “It’s enough to make us worry a little bit.”

Damaging a fetal security system

The good news about the coronavirus is that it seldom crosses the placenta, the organ tasked with protecting a developing fetus from infections and providing it with oxygen. So moms with COVID rarely give the virus to their children before birth.

That’s important, because some viruses that directly infect the fetus – such as Zika – can cause devastating birth defects, said Karin Nielsen-Saines, MD, a specialist in pediatric infectious diseases at University of California, Los Angeles.

But studies also suggest that inflammation from a mother’s COVID infection can injure the placenta, said Jeffery Goldstein, MD, an assistant professor of pathology at Northwestern University, Chicago. In a study published in American Journal of Clinical Pathology , Dr. Goldstein and his coauthors found that placentas from COVID-infected moms had more abnormal blood vessels than placentas from patients without COVID, making it harder for them to deliver sufficient oxygen to the fetus.

Placental damage can also lead to preeclampsia, a serious complication of pregnancy that can cause a mother’s blood pressure to spike.

Preeclampsia occurs when blood vessels in the placenta don’t develop or function properly, forcing the mother’s heart to work harder to get blood to the fetus, which may not receive enough oxygen and nutrients. Preeclampsia also predisposes women to heart attacks and strokes later in life.

Rewiring the immune system

In some cases, COVID also appears to rewire a baby’s immune response, Dr. Nielsen-Saines said.

In an October study in the journal Cell Reports Medicine, Dr. Nielsen-Saines and her coauthors found that infants born to people with severe COVID infections had a different mix of immune cells and proteins than other babies. None of the newborns tested positive for the coronavirus.

The immune changes are concerning, Dr. Nielsen-Saines said, because this pattern of immune cells and proteins has previously been found in infants with respiratory problems and in some cases poor neurodevelopment.

Notably, all the babies in her study appear healthy, said Dr. Nielsen-Saines, who plans to follow them for 3 years to see whether these early signals translate into developmental delays, such as problems talking, walking, or interacting with others.

“How big of a difference does any of this make in the baby?” asked Dr. Anagnostou. “We won’t know for a few years. All we can do is try to be as prepared as possible.”

Increasing the risk for boys

Boys could face higher risks from COVID, even before birth.

Males are generally more vulnerable than females as fetuses and newborns; they’re more likely to be born prematurely and to die as infants. Preterm boys also have a higher risk of disability and death.

But coronavirus infection poses special dangers, said Sabra Klein, PhD, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, Baltimore.

That’s because boys are disproportionately affected by conditions linked to maternal infections. Boys are four times as likely as girls to be diagnosed with autism or attention-deficit/hyperactivity disorder, for example, while men are 75% more likely than women to develop schizophrenia.

Scientists don’t fully understand why boys appear more fragile in the womb, although testosterone – which can dampen immune response – may play a role, said Kristina Adams Waldorf, MD, a professor of obstetrics and gynecology at the University of Washington.

Men generally mount weaker immune responses than women and more often develop severe COVID infections. Recent research suggests boys with COVID are more likely than girls to become seriously ill or develop a rare inflammatory condition called multisystem inflammatory syndrome.

New research on COVID could help illuminate this vulnerability.

In a study published in October, researchers found that the sex of a fetus influences the way its placenta responds to COVID, as well as how its mother’s immune system responds.

Pregnant people infected with COVID made fewer antibodies against the coronavirus if they were carrying male fetuses than if they were carrying females. Mothers also transferred fewer antibodies to boys than to girls, said Andrea Edlow, MD, senior author of the study and a maternal-fetal medicine specialist at Massachusetts General Hospital, Boston.

When examining the placentas of male fetuses after delivery, researchers found changes that could leave boys less protected against damaging inflammation.

The sex of a fetus can influence its mother’s response to other illnesses, as well.

For example, research shows that pregnant women with asthma have worse symptoms if they’re carrying a female. Women carrying males are slightly more likely to develop gestational diabetes.

Dr. Edlow said her findings raise questions about the “cross talk” between mother and baby. “The mom’s immune system is sensing there is a male fetus,” Dr. Edlow said. “And the fetus is actively communicating with the mom’s immune system.”

Boosting toxic stress

Rates of depression and stress among pregnant women have increased dramatically during the pandemic.

That’s concerning because chronic stress can lead to inflammation, affecting the babies of both infected and uninfected women, Dr. Anagnostou said.

Studies consistently show that infants born to mothers who experience significant stress during pregnancy have higher rates of short- and long-term health damage – including heart defects and obesity – than babies born to women with less stress.

“We know that inflammation directly influences the way a baby’s brain develops,” said Elinor Sullivan, PhD, an associate professor in psychiatry at Oregon Health & Science University, Portland.

Lockdowns, travel restrictions and physical distancing left many pregnant women without the support of family and friends. The stress of losing a loved one, a job, or a home further heightens the risks to moms and babies, said Dr. Sullivan, who is following children born during the pandemic for 5 years.

In research that has not yet been published, Dr. Sullivan found that babies of women who were pregnant during the pandemic showed more sadness and negative emotions in the first year of life, compared with infants of women who were pregnant before the pandemic.

The findings show the importance of helping and protecting pregnant people before and after delivery, said Dr. Sullivan, who conducted a separate study that found women who received more social support were less depressed.

Italian researchers are also studying the effect of maternal stress on infants’ behavior, as well as the way their genes are regulated.

Although stress-related inflammation doesn’t alter the structure of a baby’s genes, it can influence whether they’re turned on and off, said Livio Provenzi, PhD, a psychologist at the C. Mondino National Institute of Neurology Foundation in Pavia, Italy.

In Dr. Provenzi’s study of 163 mother-baby pairs he found differences in how genes that regulate the stress response were activated. Genes that help people respond to stress were more likely to be turned off in babies whose moms reported the most stress during pregnancy. The same moms also reported that their babies cried more and were fussier when they were 3 months old.

Researchers usually prefer to make in-person observations of babies as they interact with their mothers, Dr. Provenzi said. But because of the pandemic, Dr. Provenzi asked mothers to fill out questionnaires about infant behavior. He plans to observe mothers and babies in person when the children are 12 months old.

While vaccinating pregnant people is the best way to protect them and their fetuses from the virus, Dr. Anagnostou said, society needs to do more to preserve expectant mothers’ mental health.

“We can’t escape the fact that we’ve lived through 2 years of a pandemic,” Dr. Anagnostou said. “But we can think about opportunities for reducing the risk.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Tisagenlecleucel failed to outperform standard of care treatment when given as a second-line treatment for certain patients with relapsed/refractory aggressive non-Hodgkin lymphomas, according to results of a randomized, phase 3 trial.

The chimeric antigen receptor (CAR) T-cell therapy did not improve event-free survival (EFS) in this phase 3 BELINDA study, potentially because of study design decisions or imbalances in relevant patient characteristics, according to the study investigators.

Despite the negative result, insights from this study will inform the development of future clinical trials of CAR T-cell therapy, said BELINDA investigator Michael R. Bishop, MD, of the David and Etta Jonas Center for Cellular Therapy, University of Chicago.

Findings of BELINDA, presented at the annual meeting of the American Society of Hematology, stand in contrast to two other high-profile CAR T-cell therapy studies also presented at the meeting. Those other studies demonstrated significant improvements in EFS in the second-line treatment of large B-cell lymphomas.

“All of us are excited to see that the other two trials were positive, and we were hoping that ours would be as well, but there are significant differences in the trial design,” Dr. Bishop said in a press conference held at the ASH meeting.

Tisagenlecleucel (tisa-cel), an anti-CD19 CAR T-cell therapy, is already approved by the Food and Drug Administration for the treatment of patients with relapsed or refractory large B-cell lymphomas after at least two other lines of systemic therapy.

The aim of the pivotal phase 3, randomized, multicenter BELINDA study was to evaluate tisa-cel earlier in the course of treatment for patients with more aggressive disease, according to Dr. Bishop.

About two-thirds of non-Hodgkin lymphoma patients will be cured with first-line treatment. However, very poor outcomes are seen among patients with disease that does not respond to the initial treatment or that reoccurs shortly afterward, Dr. Bishop said.

The standard of care approach for those patients is second-line therapy, he noted, usually with combination chemoimmunotherapy, followed by autologous stem cell transplant if the disease responds to chemotherapy.

“Unfortunately, only a minority of those patients will be found to have chemotherapy-sensitive disease and be able to go on to autologous stem cell transplantation,” Dr. Bishop said. “And even in that subgroup of patients, the outcomes are relatively poor.”

Accordingly, the phase 3 BELINDA study enrolled patients with aggressive non-Hodgkin lymphomas that either did not respond to first-line treatment or that reoccurred within 12 months.

The primary endpoint of the study was EFS, defined as the time from randomization to either stable or progressive disease at or after a week 12 assessment or to any-cause death at any time.

While that primary endpoint was not met for tisa-cel versus standard of care therapy, two other randomized, phase 3 studies presented at the ASH meeting did demonstrate that CAR T-cell therapy extended EFS when given as a second-line lymphoma treatment.

In the randomized, phase 3 ZUMA-7 trial, axicabtagene ciloleucel (axi-cel) significantly improved EFS versus standard of care in the treatment of patients with large B-cell lymphoma refractory to or relapsed within 12 months of adequate first-line therapy, according to investigators.

Similarly, the investigators said that treatment with lisocabtagene maraleucel (liso-cel) led to a significant improvement in EFS in TRANSFORM, a randomized, phase 3 clinical trial that enrolled patients with large B-cell lymphoma that was refractory to first-line therapy or else relapsed within 12 months of that treatment.

“It’s very possible that either or both the patient characteristics and the study design is what led to the difference in the top-line study results,” lymphoma specialist Andrew M. Evens, DO, said in an interview.

There were substantial differences between the studies in terms of what was allowed as optional bridging therapy and salvage therapy, according to Dr. Evens, associate director for clinical services and director of the lymphoma program at Rutgers Cancer Institute in New Brunswick, N.J.

“In ZUMA-7, they only allowed steroids as bridging therapy,” said Dr. Evens, who was not an investigator on any of the three second-line CAR T-cell studies.

In the BELINDA study, optional platinum-based chemotherapy bridging treatment allowed in one arm of the study could have potentially delayed tisa-cel infusion until after the week 6 assessment, study investigators reported in their ASH meeting abstract.

Differences in lymphodepleting therapy prior to CAR T-cell therapy could have also played a role. According to Dr. Bishop, the total doses of cyclophosphamide and fludarabine in BELINDA were 900 mg/m2 and 75 mg/m2, respectively, while in the other two trials, doses were 1,500 mg/m² and 90 mg/m², respectively.

Lymphodepleting chemotherapy is “extremely important” in the success of CAR T-cell therapeutic approaches, he noted at the press conference.

Dr. Bishop reported receiving consultancy fees from Arcellx, Autolus Therapeutics, Bristol-Myers Squibb, CRISPR, Kite/Gilead, and Novartis. He also reported research funding from Bristol-Myers Squibb and Kite/Gilead.

Tisagenlecleucel failed to outperform standard of care treatment when given as a second-line treatment for certain patients with relapsed/refractory aggressive non-Hodgkin lymphomas, according to results of a randomized, phase 3 trial.

The chimeric antigen receptor (CAR) T-cell therapy did not improve event-free survival (EFS) in this phase 3 BELINDA study, potentially because of study design decisions or imbalances in relevant patient characteristics, according to the study investigators.

Despite the negative result, insights from this study will inform the development of future clinical trials of CAR T-cell therapy, said BELINDA investigator Michael R. Bishop, MD, of the David and Etta Jonas Center for Cellular Therapy, University of Chicago.

Findings of BELINDA, presented at the annual meeting of the American Society of Hematology, stand in contrast to two other high-profile CAR T-cell therapy studies also presented at the meeting. Those other studies demonstrated significant improvements in EFS in the second-line treatment of large B-cell lymphomas.

“All of us are excited to see that the other two trials were positive, and we were hoping that ours would be as well, but there are significant differences in the trial design,” Dr. Bishop said in a press conference held at the ASH meeting.

Tisagenlecleucel (tisa-cel), an anti-CD19 CAR T-cell therapy, is already approved by the Food and Drug Administration for the treatment of patients with relapsed or refractory large B-cell lymphomas after at least two other lines of systemic therapy.

The aim of the pivotal phase 3, randomized, multicenter BELINDA study was to evaluate tisa-cel earlier in the course of treatment for patients with more aggressive disease, according to Dr. Bishop.

About two-thirds of non-Hodgkin lymphoma patients will be cured with first-line treatment. However, very poor outcomes are seen among patients with disease that does not respond to the initial treatment or that reoccurs shortly afterward, Dr. Bishop said.

The standard of care approach for those patients is second-line therapy, he noted, usually with combination chemoimmunotherapy, followed by autologous stem cell transplant if the disease responds to chemotherapy.

“Unfortunately, only a minority of those patients will be found to have chemotherapy-sensitive disease and be able to go on to autologous stem cell transplantation,” Dr. Bishop said. “And even in that subgroup of patients, the outcomes are relatively poor.”

Accordingly, the phase 3 BELINDA study enrolled patients with aggressive non-Hodgkin lymphomas that either did not respond to first-line treatment or that reoccurred within 12 months.

The primary endpoint of the study was EFS, defined as the time from randomization to either stable or progressive disease at or after a week 12 assessment or to any-cause death at any time.

While that primary endpoint was not met for tisa-cel versus standard of care therapy, two other randomized, phase 3 studies presented at the ASH meeting did demonstrate that CAR T-cell therapy extended EFS when given as a second-line lymphoma treatment.

In the randomized, phase 3 ZUMA-7 trial, axicabtagene ciloleucel (axi-cel) significantly improved EFS versus standard of care in the treatment of patients with large B-cell lymphoma refractory to or relapsed within 12 months of adequate first-line therapy, according to investigators.

Similarly, the investigators said that treatment with lisocabtagene maraleucel (liso-cel) led to a significant improvement in EFS in TRANSFORM, a randomized, phase 3 clinical trial that enrolled patients with large B-cell lymphoma that was refractory to first-line therapy or else relapsed within 12 months of that treatment.

“It’s very possible that either or both the patient characteristics and the study design is what led to the difference in the top-line study results,” lymphoma specialist Andrew M. Evens, DO, said in an interview.

There were substantial differences between the studies in terms of what was allowed as optional bridging therapy and salvage therapy, according to Dr. Evens, associate director for clinical services and director of the lymphoma program at Rutgers Cancer Institute in New Brunswick, N.J.

“In ZUMA-7, they only allowed steroids as bridging therapy,” said Dr. Evens, who was not an investigator on any of the three second-line CAR T-cell studies.

In the BELINDA study, optional platinum-based chemotherapy bridging treatment allowed in one arm of the study could have potentially delayed tisa-cel infusion until after the week 6 assessment, study investigators reported in their ASH meeting abstract.

Differences in lymphodepleting therapy prior to CAR T-cell therapy could have also played a role. According to Dr. Bishop, the total doses of cyclophosphamide and fludarabine in BELINDA were 900 mg/m2 and 75 mg/m2, respectively, while in the other two trials, doses were 1,500 mg/m² and 90 mg/m², respectively.

Lymphodepleting chemotherapy is “extremely important” in the success of CAR T-cell therapeutic approaches, he noted at the press conference.

Dr. Bishop reported receiving consultancy fees from Arcellx, Autolus Therapeutics, Bristol-Myers Squibb, CRISPR, Kite/Gilead, and Novartis. He also reported research funding from Bristol-Myers Squibb and Kite/Gilead.

Tisagenlecleucel failed to outperform standard of care treatment when given as a second-line treatment for certain patients with relapsed/refractory aggressive non-Hodgkin lymphomas, according to results of a randomized, phase 3 trial.

The chimeric antigen receptor (CAR) T-cell therapy did not improve event-free survival (EFS) in this phase 3 BELINDA study, potentially because of study design decisions or imbalances in relevant patient characteristics, according to the study investigators.

Despite the negative result, insights from this study will inform the development of future clinical trials of CAR T-cell therapy, said BELINDA investigator Michael R. Bishop, MD, of the David and Etta Jonas Center for Cellular Therapy, University of Chicago.

Findings of BELINDA, presented at the annual meeting of the American Society of Hematology, stand in contrast to two other high-profile CAR T-cell therapy studies also presented at the meeting. Those other studies demonstrated significant improvements in EFS in the second-line treatment of large B-cell lymphomas.

“All of us are excited to see that the other two trials were positive, and we were hoping that ours would be as well, but there are significant differences in the trial design,” Dr. Bishop said in a press conference held at the ASH meeting.

Tisagenlecleucel (tisa-cel), an anti-CD19 CAR T-cell therapy, is already approved by the Food and Drug Administration for the treatment of patients with relapsed or refractory large B-cell lymphomas after at least two other lines of systemic therapy.

The aim of the pivotal phase 3, randomized, multicenter BELINDA study was to evaluate tisa-cel earlier in the course of treatment for patients with more aggressive disease, according to Dr. Bishop.

About two-thirds of non-Hodgkin lymphoma patients will be cured with first-line treatment. However, very poor outcomes are seen among patients with disease that does not respond to the initial treatment or that reoccurs shortly afterward, Dr. Bishop said.

The standard of care approach for those patients is second-line therapy, he noted, usually with combination chemoimmunotherapy, followed by autologous stem cell transplant if the disease responds to chemotherapy.

“Unfortunately, only a minority of those patients will be found to have chemotherapy-sensitive disease and be able to go on to autologous stem cell transplantation,” Dr. Bishop said. “And even in that subgroup of patients, the outcomes are relatively poor.”

Accordingly, the phase 3 BELINDA study enrolled patients with aggressive non-Hodgkin lymphomas that either did not respond to first-line treatment or that reoccurred within 12 months.

The primary endpoint of the study was EFS, defined as the time from randomization to either stable or progressive disease at or after a week 12 assessment or to any-cause death at any time.

While that primary endpoint was not met for tisa-cel versus standard of care therapy, two other randomized, phase 3 studies presented at the ASH meeting did demonstrate that CAR T-cell therapy extended EFS when given as a second-line lymphoma treatment.

In the randomized, phase 3 ZUMA-7 trial, axicabtagene ciloleucel (axi-cel) significantly improved EFS versus standard of care in the treatment of patients with large B-cell lymphoma refractory to or relapsed within 12 months of adequate first-line therapy, according to investigators.

Similarly, the investigators said that treatment with lisocabtagene maraleucel (liso-cel) led to a significant improvement in EFS in TRANSFORM, a randomized, phase 3 clinical trial that enrolled patients with large B-cell lymphoma that was refractory to first-line therapy or else relapsed within 12 months of that treatment.

“It’s very possible that either or both the patient characteristics and the study design is what led to the difference in the top-line study results,” lymphoma specialist Andrew M. Evens, DO, said in an interview.

There were substantial differences between the studies in terms of what was allowed as optional bridging therapy and salvage therapy, according to Dr. Evens, associate director for clinical services and director of the lymphoma program at Rutgers Cancer Institute in New Brunswick, N.J.

“In ZUMA-7, they only allowed steroids as bridging therapy,” said Dr. Evens, who was not an investigator on any of the three second-line CAR T-cell studies.

In the BELINDA study, optional platinum-based chemotherapy bridging treatment allowed in one arm of the study could have potentially delayed tisa-cel infusion until after the week 6 assessment, study investigators reported in their ASH meeting abstract.

Differences in lymphodepleting therapy prior to CAR T-cell therapy could have also played a role. According to Dr. Bishop, the total doses of cyclophosphamide and fludarabine in BELINDA were 900 mg/m2 and 75 mg/m2, respectively, while in the other two trials, doses were 1,500 mg/m² and 90 mg/m², respectively.

Lymphodepleting chemotherapy is “extremely important” in the success of CAR T-cell therapeutic approaches, he noted at the press conference.

Dr. Bishop reported receiving consultancy fees from Arcellx, Autolus Therapeutics, Bristol-Myers Squibb, CRISPR, Kite/Gilead, and Novartis. He also reported research funding from Bristol-Myers Squibb and Kite/Gilead.

ATLANTA – Older patients with acute lymphoblastic leukemia positive for the Philadelphia chromosome (Ph+ALL) are often not fit enough to withstand intensive chemotherapy and stem cell transplants, but remissions with alternative therapies are usually short lived.

Now, results from an ongoing study suggest that the combination of the tyrosine kinase inhibitor (TKI) dastatinib (Sprycel) with the bispecific T-cell engager (BiTE) blinatumomab (Blincyto), together with prednisone, may significantly improve remission rates and prolong both progression-free and overall survival among older and/or less fit patients with Ph+ALL.

The new results were reported by investigators in the SWOG Cancer Research Network and come from a cohort of 25 patients with a median age of 73 years with newly diagnosed Ph+ALL or ALL with dasatinib-sensitive fusions of mutations (Ph-like ALL).

Nearly all (23 of 25 patients, 92%) had complete remissions, and 5 of 16 patients for whom minimal residual disease (MRD) data were available were MRD negative at day 28, said Anjali Advani, MD, from the Cleveland Clinic.

At a median follow-up of 1.7 years, the estimated 3-year disease-free survival rate was 80%, and the estimated overall survival rate was 85%, the investigators reported in a poster presentation at the annual meeting of the American Society of Hematology.

“I think the biggest question will be longer-term follow-up. We clearly see high remission rates in this population, but the issue is whether in these elderly patients who are not candidates for chemo we can prolong remission by the addition of other treatments, such as blinatumomab,” she said in an interview with this news organization.

“The follow-up is reasonable at this point, and as we get longer follow-up, if the current 3-year survival estimates hold up, that would be very encouraging,” she said.
 

Early promise

A leukemia specialist who was not involved in the study told this news organization that the results are promising, but added that it’s too early to make definitive judgments about the efficacy of the combination.

“People have used just a tyrosine kinase inhibitor and prednisone in these patients and gotten remissions, but they just don’t last,” said Peter Emanuel, MD, from CHI St. Vincent Infirmary in Little Rock, Ark.

“The promise with this approach is that you’re getting a longer-lasting remission – maybe not a cure, but a longer-lasting remission – without having to use intensive chemotherapy,” he said.

“It’s still a pretty small study, so I think this is going to require a bigger trial, looking at more patients, but it’s certainly very encouraging and very promising,” he added.

Hanno Hock, MD, PhD, a leukemia researcher at the Mass General Cancer Center in Boston, said in an interview that “the whole idea here is to add this newer agent, blinatumomab, to make those good initial responses more durable, and it looks like it is able to do that with very impressive initial data,” he said.

“The caveat is that this is still early, and one needs to wait and see how it all pans out, but it’s very well tolerated, and definitely the next logical step in trying to offer something to people who cannot tolerate more aggressive therapy such as transplant,” Dr. Hock added.
 

Study results

The new results come from a feasibility cohort of patients enrolled in the SWOG S1318 trial, which studied blinatumomab plus chemotherapy and prednisone in older patients with Ph-ALL, as well as blinatumomab, dasatinib, and prednisone in older adults with Ph+ ALL.

Patients 65 and older with newly diagnosed or relapsed/refractory Ph+ALL or Ph-like ALL and no central nervous system disease were eligible for the arm of the trial described here. All patients with data reported in this analysis had newly diagnosed ALL.

Patients first received a single induction cycle of dasatinib and prednisone and were then evaluated for response. Patients with a complete remission (CR) or CR with incomplete recovery of blood counts (CRi) would then undergo prednisone tapering while continuing dasatinib until day 84. Patients without a CR or CRi at day 28 who had remissions by day 56 then also continued dasatinib until day 84.

Those patients still in remission at day 84 went on to three cycles of blinatumomab and dasatinib, followed by dasatinib and prednisone maintenance until unacceptable toxicity or disease progression. Patients may remain on maintenance for up to 10 years after registration.

Patients who do not have a CR or CRi by day 84 can receive reinduction with up to two total cycles of blinatumomab, with those who get a remission moving on to the blinatumomab/ dasatinib combination and those who do not going off protocol.

Of the 25 patients, 23 had a CR following dasatinib/prednisone induction. As noted, 5 of 16 patients evaluable for MRD were MRD negative.

Four patients did not receive postremission therapy, two because of adverse events, one who went on to transplant, and one because of insurance issues.

In a safety review early in the study, 4 of 12 evaluable patients were found to have dose-limiting toxicities, including one case each of grade 3 dyspnea and gastrointestinal pain (in a single patient), hypertension, dyspnea, and hyperglycemia.

These adverse events were deemed acceptable by both U.S. Food and Drug Administration and National Cancer Institute reviewers, and this arm of the study was allowed to continue, Dr. Advani noted.

The study was funded by grants from the National Institutes of Health. Dr. Advani disclosed financial relationships with several companies. Dr. Emanuel and Dr. Hock have disclosed no relevant financial relationships.

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

ATLANTA – Older patients with acute lymphoblastic leukemia positive for the Philadelphia chromosome (Ph+ALL) are often not fit enough to withstand intensive chemotherapy and stem cell transplants, but remissions with alternative therapies are usually short lived.

Now, results from an ongoing study suggest that the combination of the tyrosine kinase inhibitor (TKI) dastatinib (Sprycel) with the bispecific T-cell engager (BiTE) blinatumomab (Blincyto), together with prednisone, may significantly improve remission rates and prolong both progression-free and overall survival among older and/or less fit patients with Ph+ALL.

The new results were reported by investigators in the SWOG Cancer Research Network and come from a cohort of 25 patients with a median age of 73 years with newly diagnosed Ph+ALL or ALL with dasatinib-sensitive fusions of mutations (Ph-like ALL).

Nearly all (23 of 25 patients, 92%) had complete remissions, and 5 of 16 patients for whom minimal residual disease (MRD) data were available were MRD negative at day 28, said Anjali Advani, MD, from the Cleveland Clinic.

At a median follow-up of 1.7 years, the estimated 3-year disease-free survival rate was 80%, and the estimated overall survival rate was 85%, the investigators reported in a poster presentation at the annual meeting of the American Society of Hematology.

“I think the biggest question will be longer-term follow-up. We clearly see high remission rates in this population, but the issue is whether in these elderly patients who are not candidates for chemo we can prolong remission by the addition of other treatments, such as blinatumomab,” she said in an interview with this news organization.

“The follow-up is reasonable at this point, and as we get longer follow-up, if the current 3-year survival estimates hold up, that would be very encouraging,” she said.
 

Early promise

A leukemia specialist who was not involved in the study told this news organization that the results are promising, but added that it’s too early to make definitive judgments about the efficacy of the combination.

“People have used just a tyrosine kinase inhibitor and prednisone in these patients and gotten remissions, but they just don’t last,” said Peter Emanuel, MD, from CHI St. Vincent Infirmary in Little Rock, Ark.

“The promise with this approach is that you’re getting a longer-lasting remission – maybe not a cure, but a longer-lasting remission – without having to use intensive chemotherapy,” he said.

“It’s still a pretty small study, so I think this is going to require a bigger trial, looking at more patients, but it’s certainly very encouraging and very promising,” he added.

Hanno Hock, MD, PhD, a leukemia researcher at the Mass General Cancer Center in Boston, said in an interview that “the whole idea here is to add this newer agent, blinatumomab, to make those good initial responses more durable, and it looks like it is able to do that with very impressive initial data,” he said.

“The caveat is that this is still early, and one needs to wait and see how it all pans out, but it’s very well tolerated, and definitely the next logical step in trying to offer something to people who cannot tolerate more aggressive therapy such as transplant,” Dr. Hock added.
 

Study results

The new results come from a feasibility cohort of patients enrolled in the SWOG S1318 trial, which studied blinatumomab plus chemotherapy and prednisone in older patients with Ph-ALL, as well as blinatumomab, dasatinib, and prednisone in older adults with Ph+ ALL.

Patients 65 and older with newly diagnosed or relapsed/refractory Ph+ALL or Ph-like ALL and no central nervous system disease were eligible for the arm of the trial described here. All patients with data reported in this analysis had newly diagnosed ALL.

Patients first received a single induction cycle of dasatinib and prednisone and were then evaluated for response. Patients with a complete remission (CR) or CR with incomplete recovery of blood counts (CRi) would then undergo prednisone tapering while continuing dasatinib until day 84. Patients without a CR or CRi at day 28 who had remissions by day 56 then also continued dasatinib until day 84.

Those patients still in remission at day 84 went on to three cycles of blinatumomab and dasatinib, followed by dasatinib and prednisone maintenance until unacceptable toxicity or disease progression. Patients may remain on maintenance for up to 10 years after registration.

Patients who do not have a CR or CRi by day 84 can receive reinduction with up to two total cycles of blinatumomab, with those who get a remission moving on to the blinatumomab/ dasatinib combination and those who do not going off protocol.

Of the 25 patients, 23 had a CR following dasatinib/prednisone induction. As noted, 5 of 16 patients evaluable for MRD were MRD negative.

Four patients did not receive postremission therapy, two because of adverse events, one who went on to transplant, and one because of insurance issues.

In a safety review early in the study, 4 of 12 evaluable patients were found to have dose-limiting toxicities, including one case each of grade 3 dyspnea and gastrointestinal pain (in a single patient), hypertension, dyspnea, and hyperglycemia.

These adverse events were deemed acceptable by both U.S. Food and Drug Administration and National Cancer Institute reviewers, and this arm of the study was allowed to continue, Dr. Advani noted.

The study was funded by grants from the National Institutes of Health. Dr. Advani disclosed financial relationships with several companies. Dr. Emanuel and Dr. Hock have disclosed no relevant financial relationships.

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

ATLANTA – Older patients with acute lymphoblastic leukemia positive for the Philadelphia chromosome (Ph+ALL) are often not fit enough to withstand intensive chemotherapy and stem cell transplants, but remissions with alternative therapies are usually short lived.

Now, results from an ongoing study suggest that the combination of the tyrosine kinase inhibitor (TKI) dastatinib (Sprycel) with the bispecific T-cell engager (BiTE) blinatumomab (Blincyto), together with prednisone, may significantly improve remission rates and prolong both progression-free and overall survival among older and/or less fit patients with Ph+ALL.

The new results were reported by investigators in the SWOG Cancer Research Network and come from a cohort of 25 patients with a median age of 73 years with newly diagnosed Ph+ALL or ALL with dasatinib-sensitive fusions of mutations (Ph-like ALL).

Nearly all (23 of 25 patients, 92%) had complete remissions, and 5 of 16 patients for whom minimal residual disease (MRD) data were available were MRD negative at day 28, said Anjali Advani, MD, from the Cleveland Clinic.

At a median follow-up of 1.7 years, the estimated 3-year disease-free survival rate was 80%, and the estimated overall survival rate was 85%, the investigators reported in a poster presentation at the annual meeting of the American Society of Hematology.

“I think the biggest question will be longer-term follow-up. We clearly see high remission rates in this population, but the issue is whether in these elderly patients who are not candidates for chemo we can prolong remission by the addition of other treatments, such as blinatumomab,” she said in an interview with this news organization.

“The follow-up is reasonable at this point, and as we get longer follow-up, if the current 3-year survival estimates hold up, that would be very encouraging,” she said.
 

Early promise

A leukemia specialist who was not involved in the study told this news organization that the results are promising, but added that it’s too early to make definitive judgments about the efficacy of the combination.

“People have used just a tyrosine kinase inhibitor and prednisone in these patients and gotten remissions, but they just don’t last,” said Peter Emanuel, MD, from CHI St. Vincent Infirmary in Little Rock, Ark.

“The promise with this approach is that you’re getting a longer-lasting remission – maybe not a cure, but a longer-lasting remission – without having to use intensive chemotherapy,” he said.

“It’s still a pretty small study, so I think this is going to require a bigger trial, looking at more patients, but it’s certainly very encouraging and very promising,” he added.

Hanno Hock, MD, PhD, a leukemia researcher at the Mass General Cancer Center in Boston, said in an interview that “the whole idea here is to add this newer agent, blinatumomab, to make those good initial responses more durable, and it looks like it is able to do that with very impressive initial data,” he said.

“The caveat is that this is still early, and one needs to wait and see how it all pans out, but it’s very well tolerated, and definitely the next logical step in trying to offer something to people who cannot tolerate more aggressive therapy such as transplant,” Dr. Hock added.
 

Study results

The new results come from a feasibility cohort of patients enrolled in the SWOG S1318 trial, which studied blinatumomab plus chemotherapy and prednisone in older patients with Ph-ALL, as well as blinatumomab, dasatinib, and prednisone in older adults with Ph+ ALL.

Patients 65 and older with newly diagnosed or relapsed/refractory Ph+ALL or Ph-like ALL and no central nervous system disease were eligible for the arm of the trial described here. All patients with data reported in this analysis had newly diagnosed ALL.

Patients first received a single induction cycle of dasatinib and prednisone and were then evaluated for response. Patients with a complete remission (CR) or CR with incomplete recovery of blood counts (CRi) would then undergo prednisone tapering while continuing dasatinib until day 84. Patients without a CR or CRi at day 28 who had remissions by day 56 then also continued dasatinib until day 84.

Those patients still in remission at day 84 went on to three cycles of blinatumomab and dasatinib, followed by dasatinib and prednisone maintenance until unacceptable toxicity or disease progression. Patients may remain on maintenance for up to 10 years after registration.

Patients who do not have a CR or CRi by day 84 can receive reinduction with up to two total cycles of blinatumomab, with those who get a remission moving on to the blinatumomab/ dasatinib combination and those who do not going off protocol.

Of the 25 patients, 23 had a CR following dasatinib/prednisone induction. As noted, 5 of 16 patients evaluable for MRD were MRD negative.

Four patients did not receive postremission therapy, two because of adverse events, one who went on to transplant, and one because of insurance issues.

In a safety review early in the study, 4 of 12 evaluable patients were found to have dose-limiting toxicities, including one case each of grade 3 dyspnea and gastrointestinal pain (in a single patient), hypertension, dyspnea, and hyperglycemia.

These adverse events were deemed acceptable by both U.S. Food and Drug Administration and National Cancer Institute reviewers, and this arm of the study was allowed to continue, Dr. Advani noted.

The study was funded by grants from the National Institutes of Health. Dr. Advani disclosed financial relationships with several companies. Dr. Emanuel and Dr. Hock have disclosed no relevant financial relationships.

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

Louisiana Gov. John Bel Edwards says the state government plans to make the COVID-19 vaccine a required immunization for students 16 and older in the state’s public school system.

“I just think it’s really, really important to embrace the science and really it’s also important to not engage in misinformation,” said Gov. Edwards, a Democrat, according to The Advocate. “Absent some compelling reason, which I at present have not seen, I fully expect that we will be adding the vaccine to the schedule.”

Parents could opt out their children from the requirement with a letter from a medical provider or a simple signature in dissent, The Advocate reported. The new rule would go into effect at the start of the 2022 school year and at first would apply to students aged 16 and older.

Republican legislators voiced their opposition to the COVID-19 vaccine requirement at a hearing on Dec. 6, calling it unneeded and an example of governmental overreach.

“I believe the vaccine should be highly recommended but not mandated,” state Rep. Laurie Schlegel said, according to TV station WDSU.

State Sen. Cameron Henry of Metairie said he received “hundreds of emails” from parents asking him to prevent the rule from going into effect, WDSU said.

WDSU said the governor can overrule the committee if it rejects the proposed vaccine rule.

Louisiana State Health Officer Joseph Kanter, MD, testified on Dec. 6 that 18 children had died of COVID-19 in Louisiana and many others had become sick because of it.

“I can’t think of another disease on that childhood schedule that we’ve lost that many kids from. In my mind, it’s very much in the public interest. But it’s the family and the parents’ decision,” Dr. Kanter said.

The addition of the vaccine is being proposed by the Louisiana Department of Health, which has added other vaccines to the required list over the years. In 2015, the legislature added meningitis as a required shot with no controversy, The Advocate said.

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

Louisiana Gov. John Bel Edwards says the state government plans to make the COVID-19 vaccine a required immunization for students 16 and older in the state’s public school system.

“I just think it’s really, really important to embrace the science and really it’s also important to not engage in misinformation,” said Gov. Edwards, a Democrat, according to The Advocate. “Absent some compelling reason, which I at present have not seen, I fully expect that we will be adding the vaccine to the schedule.”

Parents could opt out their children from the requirement with a letter from a medical provider or a simple signature in dissent, The Advocate reported. The new rule would go into effect at the start of the 2022 school year and at first would apply to students aged 16 and older.

Republican legislators voiced their opposition to the COVID-19 vaccine requirement at a hearing on Dec. 6, calling it unneeded and an example of governmental overreach.

“I believe the vaccine should be highly recommended but not mandated,” state Rep. Laurie Schlegel said, according to TV station WDSU.

State Sen. Cameron Henry of Metairie said he received “hundreds of emails” from parents asking him to prevent the rule from going into effect, WDSU said.

WDSU said the governor can overrule the committee if it rejects the proposed vaccine rule.

Louisiana State Health Officer Joseph Kanter, MD, testified on Dec. 6 that 18 children had died of COVID-19 in Louisiana and many others had become sick because of it.

“I can’t think of another disease on that childhood schedule that we’ve lost that many kids from. In my mind, it’s very much in the public interest. But it’s the family and the parents’ decision,” Dr. Kanter said.

The addition of the vaccine is being proposed by the Louisiana Department of Health, which has added other vaccines to the required list over the years. In 2015, the legislature added meningitis as a required shot with no controversy, The Advocate said.

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

Louisiana Gov. John Bel Edwards says the state government plans to make the COVID-19 vaccine a required immunization for students 16 and older in the state’s public school system.

“I just think it’s really, really important to embrace the science and really it’s also important to not engage in misinformation,” said Gov. Edwards, a Democrat, according to The Advocate. “Absent some compelling reason, which I at present have not seen, I fully expect that we will be adding the vaccine to the schedule.”

Parents could opt out their children from the requirement with a letter from a medical provider or a simple signature in dissent, The Advocate reported. The new rule would go into effect at the start of the 2022 school year and at first would apply to students aged 16 and older.

Republican legislators voiced their opposition to the COVID-19 vaccine requirement at a hearing on Dec. 6, calling it unneeded and an example of governmental overreach.

“I believe the vaccine should be highly recommended but not mandated,” state Rep. Laurie Schlegel said, according to TV station WDSU.

State Sen. Cameron Henry of Metairie said he received “hundreds of emails” from parents asking him to prevent the rule from going into effect, WDSU said.

WDSU said the governor can overrule the committee if it rejects the proposed vaccine rule.

Louisiana State Health Officer Joseph Kanter, MD, testified on Dec. 6 that 18 children had died of COVID-19 in Louisiana and many others had become sick because of it.

“I can’t think of another disease on that childhood schedule that we’ve lost that many kids from. In my mind, it’s very much in the public interest. But it’s the family and the parents’ decision,” Dr. Kanter said.

The addition of the vaccine is being proposed by the Louisiana Department of Health, which has added other vaccines to the required list over the years. In 2015, the legislature added meningitis as a required shot with no controversy, The Advocate said.

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

An updated analysis of the phase 3 CheckMate 067 trial confirms the durability of combination immunotherapy for metastatic melanoma, representing a “substantial development” in treatment, researchers say.

Nearly half the patients treated with nivolumab (Opdivo) and ipilimumab (Yervoy) were alive at 6½ years. Within this group, 77% had not received further systemic treatment after coming off the study drugs.

After a minimum follow-up of 77 months, median overall survival was 72.1 months in patients on the combination, which was more than three times longer than the 19.9 months with ipilimumab alone (hazard ratio, 0.52; 95% confidence interval, 0.43-0.64) and twice as long as the 36.9 months with nivolumab alone (HR, 0.84; 95% CI, 0.67-1.04).

The results represent the longest median overall survival seen in a phase 3 trial of advanced melanoma and are evidence of “a substantial development in the melanoma treatment landscape versus the standard median survival of 8 months a decade ago,” researchers wrote in a study published online in the Journal of Clinical Oncology.

However, lead author Jedd D. Wolchok, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, noted that the study was not designed to compare nivolumab alone with the combination. “It wasn’t powered for that. [But] what we can say is that the highest survival was in the combination group,” Dr. Wolchok told this news organization.

Dr. Wolchok cautioned that the combination therapy is not currently standard of care. “PD-1 blockade – either nivolumab or the combination – are both excellent options for care,” he added. “I can’t tell you that one of them is the standard of care because that’s too complex of a decision.”

For example, he explained, “for a patient who only has lung metastases, a single-agent PD-1 blockade might be sufficient. But if it has spread to other organs, such as the liver or bones, which are more difficult to treat, that’s when we often reach for the combination.”

Other factors that weigh into the therapeutic decision are the patient’s performance status and their so-called clinical reserve for tolerating side effects. “The likelihood of having a high-grade side effect with the combination is more than twice that of the single agent,” Dr. Wolchok said.

Until 2011, only two therapies were approved for metastatic melanoma: Chemotherapy with dacarbazine and immunotherapy with high-dose interleukin-2, neither of which was very effective at prolonging life. But patient survival changed with the advent of targeted therapies and immunotherapy. Some patients are now living for years, and as the current study shows, many have surpassed the 5-year mark and are treatment free.

The updated CheckMate 067 analysis included patients with previously untreated, unresectable stage III/IV melanoma who were randomly assigned to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (four doses) followed by nivolumab 3 mg/kg every 2 weeks (n = 314), nivolumab 3 mg/kg every 2 weeks (n = 316), or ipilimumab 3 mg/ kg every 3 weeks (four doses; n = 315).

The authors reported the 5-year overall survival rates from the trial, published in the New England Journal of Medicine in 2019 – 52% with the combination, 44% with nivolumab alone, and 26% with ipilimumab alone.

In the updated study, overall survival at 6½ years had dropped slightly to 49%, 42%, and 23%, respectively. Patients with BRAF-mutant tumors had overall survival rates of 57%, 43%, and 25% versus 46%, 42%, and 22% in those with BRAF wild-type tumors.

Overall, median investigator-assessed progression-free survival was 11.5 months with the combination, 6.9 months with nivolumab alone, and 2.9 months with ipilimumab.

The new analysis also evaluated melanoma-specific survival (MSS), which removes competing causes of deaths from the long-term follow-up. The MSS was not reached in the combination group, and was 58.7 months in the nivolumab group and 21.9 months for ipilimumab, with MSS rates at 6.5 years of 56%, 48%, and 27%, respectively.

No new safety signals were detected, but there was more immune-mediated toxicity in the combination group, the researchers reported.

“The patients will continue to be followed,” said Dr. Wolchok, “And data are still being collected.”

The trial was supported by Bristol-Myers Squibb, the National Cancer Institute, and the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre. Dr. Wolchok and coauthors reported relationships with Bristol-Myers Squibb and other drugmakers.
 

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

An updated analysis of the phase 3 CheckMate 067 trial confirms the durability of combination immunotherapy for metastatic melanoma, representing a “substantial development” in treatment, researchers say.

Nearly half the patients treated with nivolumab (Opdivo) and ipilimumab (Yervoy) were alive at 6½ years. Within this group, 77% had not received further systemic treatment after coming off the study drugs.

After a minimum follow-up of 77 months, median overall survival was 72.1 months in patients on the combination, which was more than three times longer than the 19.9 months with ipilimumab alone (hazard ratio, 0.52; 95% confidence interval, 0.43-0.64) and twice as long as the 36.9 months with nivolumab alone (HR, 0.84; 95% CI, 0.67-1.04).

The results represent the longest median overall survival seen in a phase 3 trial of advanced melanoma and are evidence of “a substantial development in the melanoma treatment landscape versus the standard median survival of 8 months a decade ago,” researchers wrote in a study published online in the Journal of Clinical Oncology.

However, lead author Jedd D. Wolchok, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, noted that the study was not designed to compare nivolumab alone with the combination. “It wasn’t powered for that. [But] what we can say is that the highest survival was in the combination group,” Dr. Wolchok told this news organization.

Dr. Wolchok cautioned that the combination therapy is not currently standard of care. “PD-1 blockade – either nivolumab or the combination – are both excellent options for care,” he added. “I can’t tell you that one of them is the standard of care because that’s too complex of a decision.”

For example, he explained, “for a patient who only has lung metastases, a single-agent PD-1 blockade might be sufficient. But if it has spread to other organs, such as the liver or bones, which are more difficult to treat, that’s when we often reach for the combination.”

Other factors that weigh into the therapeutic decision are the patient’s performance status and their so-called clinical reserve for tolerating side effects. “The likelihood of having a high-grade side effect with the combination is more than twice that of the single agent,” Dr. Wolchok said.

Until 2011, only two therapies were approved for metastatic melanoma: Chemotherapy with dacarbazine and immunotherapy with high-dose interleukin-2, neither of which was very effective at prolonging life. But patient survival changed with the advent of targeted therapies and immunotherapy. Some patients are now living for years, and as the current study shows, many have surpassed the 5-year mark and are treatment free.

The updated CheckMate 067 analysis included patients with previously untreated, unresectable stage III/IV melanoma who were randomly assigned to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (four doses) followed by nivolumab 3 mg/kg every 2 weeks (n = 314), nivolumab 3 mg/kg every 2 weeks (n = 316), or ipilimumab 3 mg/ kg every 3 weeks (four doses; n = 315).

The authors reported the 5-year overall survival rates from the trial, published in the New England Journal of Medicine in 2019 – 52% with the combination, 44% with nivolumab alone, and 26% with ipilimumab alone.

In the updated study, overall survival at 6½ years had dropped slightly to 49%, 42%, and 23%, respectively. Patients with BRAF-mutant tumors had overall survival rates of 57%, 43%, and 25% versus 46%, 42%, and 22% in those with BRAF wild-type tumors.

Overall, median investigator-assessed progression-free survival was 11.5 months with the combination, 6.9 months with nivolumab alone, and 2.9 months with ipilimumab.

The new analysis also evaluated melanoma-specific survival (MSS), which removes competing causes of deaths from the long-term follow-up. The MSS was not reached in the combination group, and was 58.7 months in the nivolumab group and 21.9 months for ipilimumab, with MSS rates at 6.5 years of 56%, 48%, and 27%, respectively.

No new safety signals were detected, but there was more immune-mediated toxicity in the combination group, the researchers reported.

“The patients will continue to be followed,” said Dr. Wolchok, “And data are still being collected.”

The trial was supported by Bristol-Myers Squibb, the National Cancer Institute, and the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre. Dr. Wolchok and coauthors reported relationships with Bristol-Myers Squibb and other drugmakers.
 

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

An updated analysis of the phase 3 CheckMate 067 trial confirms the durability of combination immunotherapy for metastatic melanoma, representing a “substantial development” in treatment, researchers say.

Nearly half the patients treated with nivolumab (Opdivo) and ipilimumab (Yervoy) were alive at 6½ years. Within this group, 77% had not received further systemic treatment after coming off the study drugs.

After a minimum follow-up of 77 months, median overall survival was 72.1 months in patients on the combination, which was more than three times longer than the 19.9 months with ipilimumab alone (hazard ratio, 0.52; 95% confidence interval, 0.43-0.64) and twice as long as the 36.9 months with nivolumab alone (HR, 0.84; 95% CI, 0.67-1.04).

The results represent the longest median overall survival seen in a phase 3 trial of advanced melanoma and are evidence of “a substantial development in the melanoma treatment landscape versus the standard median survival of 8 months a decade ago,” researchers wrote in a study published online in the Journal of Clinical Oncology.

However, lead author Jedd D. Wolchok, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, noted that the study was not designed to compare nivolumab alone with the combination. “It wasn’t powered for that. [But] what we can say is that the highest survival was in the combination group,” Dr. Wolchok told this news organization.

Dr. Wolchok cautioned that the combination therapy is not currently standard of care. “PD-1 blockade – either nivolumab or the combination – are both excellent options for care,” he added. “I can’t tell you that one of them is the standard of care because that’s too complex of a decision.”

For example, he explained, “for a patient who only has lung metastases, a single-agent PD-1 blockade might be sufficient. But if it has spread to other organs, such as the liver or bones, which are more difficult to treat, that’s when we often reach for the combination.”

Other factors that weigh into the therapeutic decision are the patient’s performance status and their so-called clinical reserve for tolerating side effects. “The likelihood of having a high-grade side effect with the combination is more than twice that of the single agent,” Dr. Wolchok said.

Until 2011, only two therapies were approved for metastatic melanoma: Chemotherapy with dacarbazine and immunotherapy with high-dose interleukin-2, neither of which was very effective at prolonging life. But patient survival changed with the advent of targeted therapies and immunotherapy. Some patients are now living for years, and as the current study shows, many have surpassed the 5-year mark and are treatment free.

The updated CheckMate 067 analysis included patients with previously untreated, unresectable stage III/IV melanoma who were randomly assigned to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (four doses) followed by nivolumab 3 mg/kg every 2 weeks (n = 314), nivolumab 3 mg/kg every 2 weeks (n = 316), or ipilimumab 3 mg/ kg every 3 weeks (four doses; n = 315).

The authors reported the 5-year overall survival rates from the trial, published in the New England Journal of Medicine in 2019 – 52% with the combination, 44% with nivolumab alone, and 26% with ipilimumab alone.

In the updated study, overall survival at 6½ years had dropped slightly to 49%, 42%, and 23%, respectively. Patients with BRAF-mutant tumors had overall survival rates of 57%, 43%, and 25% versus 46%, 42%, and 22% in those with BRAF wild-type tumors.

Overall, median investigator-assessed progression-free survival was 11.5 months with the combination, 6.9 months with nivolumab alone, and 2.9 months with ipilimumab.

The new analysis also evaluated melanoma-specific survival (MSS), which removes competing causes of deaths from the long-term follow-up. The MSS was not reached in the combination group, and was 58.7 months in the nivolumab group and 21.9 months for ipilimumab, with MSS rates at 6.5 years of 56%, 48%, and 27%, respectively.

No new safety signals were detected, but there was more immune-mediated toxicity in the combination group, the researchers reported.

“The patients will continue to be followed,” said Dr. Wolchok, “And data are still being collected.”

The trial was supported by Bristol-Myers Squibb, the National Cancer Institute, and the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre. Dr. Wolchok and coauthors reported relationships with Bristol-Myers Squibb and other drugmakers.
 

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

Sleep apnea and other types of sleep disorders appear to elevate the risk for some types of cancer, specifically prostate cancer, more so than others. But the overall risk can be highly variable, and some sleep problems were found to be associated with a lower risk for cancer and cancer-related death, an analysis of a large observational cohort study of cardiovascular patients found.

Results of the analysis were published online in the journal Cancer Epidemiology. Investigators analyzed the presence of sleep apnea and insomnia and cancer risk in more than 8,500 patients in the Cardiovascular Health Study (CHS). “The fact that we observed certain sleep problems, like apneas, to be associated with elevated risk of some cancers but not others reflects the fact that cancer is a heterogeneous disease,” senior author Amanda Phipps, PhD, said in an interview. Dr. Phipps is an associate professor of epidemiology at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle.
 

Variable cancer links

The researchers assessed sleep problems in two groups in the CHS: an incident cancer group of 3,930 patients and a cancer mortality group of 4,580 patients. Within those respective groups, the investigators identified 885 first-incident cancers and 804 cancer deaths with a median follow-up of 12 and 14 years. The average age of the study population was 73 years, and 57% were women.

Sleep apnea symptoms (SAS) were associated with a lower risk for incident cancers – a 16% lower baseline risk and a 24% lower time-dependent risk. The study showed no association between cancer incidence and daytime sleepiness and apneas.

However, there was a significantly elevated risk relationship between sleep problems and prostate cancer. A time-dependent analysis of apnea showed more than double the risk (hazard ratio, 2.34), and baseline snoring carried a 69% greater risk. There was also a dose-response relationship for baseline cumulative SAS, compared with not having symptoms: an HR of 1.30 for one symptom, and 2.22 for two or more symptoms.

Risks for lymphatic or hematopoietic cancers were also associated with baseline daytime sleepiness (HR, 1.81), but not with insomnia (HR, 0.54).

With regard to cancer mortality, the study found no relationship between sleep problems and cancer death. In fact, it found an overall inverse relationship with snoring (time-dependent HR, 0.73; cumulative average HR, 0.67) and baseline apnea (HR, 0.69). Likewise, patients reporting SAS had lower risks than those having no SAS: an HR of 0.90 for one symptom and 0.75 for multiple symptoms. No relationships were found between any insomnia symptom and cancer death.

“We know the pathways that lead to prostate cancer can be very different than the pathways that lead to colorectal cancer,” Dr. Phipps said. “What we don’t yet understand is why these associations differ or what mechanisms are responsible for these cancer site-specific associations.”
 

Need for sleep assessment

The findings don’t change much for how clinicians should evaluate cancer risks in patients with sleep problems, Dr. Phipps said. “Other studies have clearly demonstrated the implications that sleep apnea has for a variety of other important health conditions – such as cardiovascular disease – so there are already plenty of good reasons for clinicians to ask their patients about their sleep and to connect patients with resources for the diagnosis and treatment of sleep apnea,” she added. “This study provides another possible reason.”

These findings provide context for future studies of the relationship between sleep problems and cancer. “But, given that sleep is something we all do and given that sleep problems are so pervasive, it’s important that we keep trying to better understand this relationship,” Dr. Phipps said.

“My hope is that future cancer studies will build in more detailed, longitudinal information on sleep patterns to help us fill current gaps in knowledge.”

Dr. Phipps has disclosed no relevant financial relationships.

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

Sleep apnea and other types of sleep disorders appear to elevate the risk for some types of cancer, specifically prostate cancer, more so than others. But the overall risk can be highly variable, and some sleep problems were found to be associated with a lower risk for cancer and cancer-related death, an analysis of a large observational cohort study of cardiovascular patients found.

Results of the analysis were published online in the journal Cancer Epidemiology. Investigators analyzed the presence of sleep apnea and insomnia and cancer risk in more than 8,500 patients in the Cardiovascular Health Study (CHS). “The fact that we observed certain sleep problems, like apneas, to be associated with elevated risk of some cancers but not others reflects the fact that cancer is a heterogeneous disease,” senior author Amanda Phipps, PhD, said in an interview. Dr. Phipps is an associate professor of epidemiology at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle.
 

Variable cancer links

The researchers assessed sleep problems in two groups in the CHS: an incident cancer group of 3,930 patients and a cancer mortality group of 4,580 patients. Within those respective groups, the investigators identified 885 first-incident cancers and 804 cancer deaths with a median follow-up of 12 and 14 years. The average age of the study population was 73 years, and 57% were women.

Sleep apnea symptoms (SAS) were associated with a lower risk for incident cancers – a 16% lower baseline risk and a 24% lower time-dependent risk. The study showed no association between cancer incidence and daytime sleepiness and apneas.

However, there was a significantly elevated risk relationship between sleep problems and prostate cancer. A time-dependent analysis of apnea showed more than double the risk (hazard ratio, 2.34), and baseline snoring carried a 69% greater risk. There was also a dose-response relationship for baseline cumulative SAS, compared with not having symptoms: an HR of 1.30 for one symptom, and 2.22 for two or more symptoms.

Risks for lymphatic or hematopoietic cancers were also associated with baseline daytime sleepiness (HR, 1.81), but not with insomnia (HR, 0.54).

With regard to cancer mortality, the study found no relationship between sleep problems and cancer death. In fact, it found an overall inverse relationship with snoring (time-dependent HR, 0.73; cumulative average HR, 0.67) and baseline apnea (HR, 0.69). Likewise, patients reporting SAS had lower risks than those having no SAS: an HR of 0.90 for one symptom and 0.75 for multiple symptoms. No relationships were found between any insomnia symptom and cancer death.

“We know the pathways that lead to prostate cancer can be very different than the pathways that lead to colorectal cancer,” Dr. Phipps said. “What we don’t yet understand is why these associations differ or what mechanisms are responsible for these cancer site-specific associations.”
 

Need for sleep assessment

The findings don’t change much for how clinicians should evaluate cancer risks in patients with sleep problems, Dr. Phipps said. “Other studies have clearly demonstrated the implications that sleep apnea has for a variety of other important health conditions – such as cardiovascular disease – so there are already plenty of good reasons for clinicians to ask their patients about their sleep and to connect patients with resources for the diagnosis and treatment of sleep apnea,” she added. “This study provides another possible reason.”

These findings provide context for future studies of the relationship between sleep problems and cancer. “But, given that sleep is something we all do and given that sleep problems are so pervasive, it’s important that we keep trying to better understand this relationship,” Dr. Phipps said.

“My hope is that future cancer studies will build in more detailed, longitudinal information on sleep patterns to help us fill current gaps in knowledge.”

Dr. Phipps has disclosed no relevant financial relationships.

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

Sleep apnea and other types of sleep disorders appear to elevate the risk for some types of cancer, specifically prostate cancer, more so than others. But the overall risk can be highly variable, and some sleep problems were found to be associated with a lower risk for cancer and cancer-related death, an analysis of a large observational cohort study of cardiovascular patients found.

Results of the analysis were published online in the journal Cancer Epidemiology. Investigators analyzed the presence of sleep apnea and insomnia and cancer risk in more than 8,500 patients in the Cardiovascular Health Study (CHS). “The fact that we observed certain sleep problems, like apneas, to be associated with elevated risk of some cancers but not others reflects the fact that cancer is a heterogeneous disease,” senior author Amanda Phipps, PhD, said in an interview. Dr. Phipps is an associate professor of epidemiology at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle.
 

Variable cancer links

The researchers assessed sleep problems in two groups in the CHS: an incident cancer group of 3,930 patients and a cancer mortality group of 4,580 patients. Within those respective groups, the investigators identified 885 first-incident cancers and 804 cancer deaths with a median follow-up of 12 and 14 years. The average age of the study population was 73 years, and 57% were women.

Sleep apnea symptoms (SAS) were associated with a lower risk for incident cancers – a 16% lower baseline risk and a 24% lower time-dependent risk. The study showed no association between cancer incidence and daytime sleepiness and apneas.

However, there was a significantly elevated risk relationship between sleep problems and prostate cancer. A time-dependent analysis of apnea showed more than double the risk (hazard ratio, 2.34), and baseline snoring carried a 69% greater risk. There was also a dose-response relationship for baseline cumulative SAS, compared with not having symptoms: an HR of 1.30 for one symptom, and 2.22 for two or more symptoms.

Risks for lymphatic or hematopoietic cancers were also associated with baseline daytime sleepiness (HR, 1.81), but not with insomnia (HR, 0.54).

With regard to cancer mortality, the study found no relationship between sleep problems and cancer death. In fact, it found an overall inverse relationship with snoring (time-dependent HR, 0.73; cumulative average HR, 0.67) and baseline apnea (HR, 0.69). Likewise, patients reporting SAS had lower risks than those having no SAS: an HR of 0.90 for one symptom and 0.75 for multiple symptoms. No relationships were found between any insomnia symptom and cancer death.

“We know the pathways that lead to prostate cancer can be very different than the pathways that lead to colorectal cancer,” Dr. Phipps said. “What we don’t yet understand is why these associations differ or what mechanisms are responsible for these cancer site-specific associations.”
 

Need for sleep assessment

The findings don’t change much for how clinicians should evaluate cancer risks in patients with sleep problems, Dr. Phipps said. “Other studies have clearly demonstrated the implications that sleep apnea has for a variety of other important health conditions – such as cardiovascular disease – so there are already plenty of good reasons for clinicians to ask their patients about their sleep and to connect patients with resources for the diagnosis and treatment of sleep apnea,” she added. “This study provides another possible reason.”

These findings provide context for future studies of the relationship between sleep problems and cancer. “But, given that sleep is something we all do and given that sleep problems are so pervasive, it’s important that we keep trying to better understand this relationship,” Dr. Phipps said.

“My hope is that future cancer studies will build in more detailed, longitudinal information on sleep patterns to help us fill current gaps in knowledge.”

Dr. Phipps has disclosed no relevant financial relationships.

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

A new analysis of over 22,000 mastectomy patients confirms what smaller studies have indicated: Patients who undergo nipple-sparing mastectomy have overall and disease-free survival similar to that of those who receive a total mastectomy.

When nipple-sparing mastectomy was introduced, many experts felt uneasy about opting for the less invasive procedure, recalled Rosa Hwang, MD, associate medical director for breast surgery at MD Anderson Cancer Center in Houston. “The concern was leaving all this skin,” said Dr. Hwang. “Are you going to leave cancer behind” and increase the risk of local recurrence?

Over the past 2 decades, the number of patients undergoing nipple-sparing mastectomy increased and, in turn, studies began to demonstrate the safety of the procedure.

However, large analyses evaluating long-term outcomes – namely, overall survival and breast cancer-specific survival – of nipple-sparing mastectomy were still lacking.

The latest study, published online Nov. 20 in Annals of Surgical Oncology, compared the long-term prognosis and survival benefits of nipple-sparing to total mastectomy in thousands of women. The analysis, which pulled data from the SEER cancer database, included 5,765 patients who underwent the nipple-sparing procedure and 17,289 patients who had a total mastectomy.

The authors found that overall survival and breast cancer–specific survival were similar for women undergoing nipple-sparing mastectomy and those receiving a total mastectomy. In fact, over the long-term, the nipple-sparing group slightly edged out the total mastectomy group in overall survival (94.61% vs. 93% at 5 years and 86.34% vs. 83.48% at 10 years, respectively) and in breast cancer-specific survival rates (96.16% vs. 95.74% at 5 years, and 92.2% vs. 91.37% at 10 years). The differences, however, were not significant.

The study also found that certain subgroups – including White women, women over age 46, those with a median household income of $70,000 or more, hormone receptor-positive, and HER2 negative – had significantly better overall survival rate with the nipple-sparing procedure (P < .05). However, the authors noted, the survival advantage in the nipple-sparing group did not extend to breast cancer–specific survival.

Dr. Hwang, who was not involved in the current analysis, said the significant overall survival result in the subgroup analysis was surprising because “there’s no biological reason why one would expect that to be true.”  

Given that the subgroups did not demonstrate better breast cancer–specific survival, Dr. Hwang believes the overall survival finding may have more to do with comorbidities, which the study did not account for, than type of mastectomy.

When choosing who is eligible for a nipple-sparing mastectomy, “We’re more selective,” Dr. Hwang said. For instance, patients with uncontrolled diabetes or who smoke are unlikely to be candidates. “So, I think it’s possible that medical comorbidities and medical conditions between these groups [were] different.”

According to the authors, coding inconsistencies represent another possible weakness of the study. From 1998 to 2010, “the term ‘nipple-sparing mastectomy’ was coded as a [total mastectomy] with the ‘subcutaneous mastectomy’ code.” It’s possible that some patients receiving the nipple-sparing procedure before 2011 were not appropriately coded in the current study.

Moving forward, a large prospective study that includes comorbidities would be helpful, but overall the study helps validate that “nipple-sparing mastectomy is a safe operation for selected patients,” Dr. Hwang said. 

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

A new analysis of over 22,000 mastectomy patients confirms what smaller studies have indicated: Patients who undergo nipple-sparing mastectomy have overall and disease-free survival similar to that of those who receive a total mastectomy.

When nipple-sparing mastectomy was introduced, many experts felt uneasy about opting for the less invasive procedure, recalled Rosa Hwang, MD, associate medical director for breast surgery at MD Anderson Cancer Center in Houston. “The concern was leaving all this skin,” said Dr. Hwang. “Are you going to leave cancer behind” and increase the risk of local recurrence?

Over the past 2 decades, the number of patients undergoing nipple-sparing mastectomy increased and, in turn, studies began to demonstrate the safety of the procedure.

However, large analyses evaluating long-term outcomes – namely, overall survival and breast cancer-specific survival – of nipple-sparing mastectomy were still lacking.

The latest study, published online Nov. 20 in Annals of Surgical Oncology, compared the long-term prognosis and survival benefits of nipple-sparing to total mastectomy in thousands of women. The analysis, which pulled data from the SEER cancer database, included 5,765 patients who underwent the nipple-sparing procedure and 17,289 patients who had a total mastectomy.

The authors found that overall survival and breast cancer–specific survival were similar for women undergoing nipple-sparing mastectomy and those receiving a total mastectomy. In fact, over the long-term, the nipple-sparing group slightly edged out the total mastectomy group in overall survival (94.61% vs. 93% at 5 years and 86.34% vs. 83.48% at 10 years, respectively) and in breast cancer-specific survival rates (96.16% vs. 95.74% at 5 years, and 92.2% vs. 91.37% at 10 years). The differences, however, were not significant.

The study also found that certain subgroups – including White women, women over age 46, those with a median household income of $70,000 or more, hormone receptor-positive, and HER2 negative – had significantly better overall survival rate with the nipple-sparing procedure (P < .05). However, the authors noted, the survival advantage in the nipple-sparing group did not extend to breast cancer–specific survival.

Dr. Hwang, who was not involved in the current analysis, said the significant overall survival result in the subgroup analysis was surprising because “there’s no biological reason why one would expect that to be true.”  

Given that the subgroups did not demonstrate better breast cancer–specific survival, Dr. Hwang believes the overall survival finding may have more to do with comorbidities, which the study did not account for, than type of mastectomy.

When choosing who is eligible for a nipple-sparing mastectomy, “We’re more selective,” Dr. Hwang said. For instance, patients with uncontrolled diabetes or who smoke are unlikely to be candidates. “So, I think it’s possible that medical comorbidities and medical conditions between these groups [were] different.”

According to the authors, coding inconsistencies represent another possible weakness of the study. From 1998 to 2010, “the term ‘nipple-sparing mastectomy’ was coded as a [total mastectomy] with the ‘subcutaneous mastectomy’ code.” It’s possible that some patients receiving the nipple-sparing procedure before 2011 were not appropriately coded in the current study.

Moving forward, a large prospective study that includes comorbidities would be helpful, but overall the study helps validate that “nipple-sparing mastectomy is a safe operation for selected patients,” Dr. Hwang said. 

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

A new analysis of over 22,000 mastectomy patients confirms what smaller studies have indicated: Patients who undergo nipple-sparing mastectomy have overall and disease-free survival similar to that of those who receive a total mastectomy.

When nipple-sparing mastectomy was introduced, many experts felt uneasy about opting for the less invasive procedure, recalled Rosa Hwang, MD, associate medical director for breast surgery at MD Anderson Cancer Center in Houston. “The concern was leaving all this skin,” said Dr. Hwang. “Are you going to leave cancer behind” and increase the risk of local recurrence?

Over the past 2 decades, the number of patients undergoing nipple-sparing mastectomy increased and, in turn, studies began to demonstrate the safety of the procedure.

However, large analyses evaluating long-term outcomes – namely, overall survival and breast cancer-specific survival – of nipple-sparing mastectomy were still lacking.

The latest study, published online Nov. 20 in Annals of Surgical Oncology, compared the long-term prognosis and survival benefits of nipple-sparing to total mastectomy in thousands of women. The analysis, which pulled data from the SEER cancer database, included 5,765 patients who underwent the nipple-sparing procedure and 17,289 patients who had a total mastectomy.

The authors found that overall survival and breast cancer–specific survival were similar for women undergoing nipple-sparing mastectomy and those receiving a total mastectomy. In fact, over the long-term, the nipple-sparing group slightly edged out the total mastectomy group in overall survival (94.61% vs. 93% at 5 years and 86.34% vs. 83.48% at 10 years, respectively) and in breast cancer-specific survival rates (96.16% vs. 95.74% at 5 years, and 92.2% vs. 91.37% at 10 years). The differences, however, were not significant.

The study also found that certain subgroups – including White women, women over age 46, those with a median household income of $70,000 or more, hormone receptor-positive, and HER2 negative – had significantly better overall survival rate with the nipple-sparing procedure (P < .05). However, the authors noted, the survival advantage in the nipple-sparing group did not extend to breast cancer–specific survival.

Dr. Hwang, who was not involved in the current analysis, said the significant overall survival result in the subgroup analysis was surprising because “there’s no biological reason why one would expect that to be true.”  

Given that the subgroups did not demonstrate better breast cancer–specific survival, Dr. Hwang believes the overall survival finding may have more to do with comorbidities, which the study did not account for, than type of mastectomy.

When choosing who is eligible for a nipple-sparing mastectomy, “We’re more selective,” Dr. Hwang said. For instance, patients with uncontrolled diabetes or who smoke are unlikely to be candidates. “So, I think it’s possible that medical comorbidities and medical conditions between these groups [were] different.”

According to the authors, coding inconsistencies represent another possible weakness of the study. From 1998 to 2010, “the term ‘nipple-sparing mastectomy’ was coded as a [total mastectomy] with the ‘subcutaneous mastectomy’ code.” It’s possible that some patients receiving the nipple-sparing procedure before 2011 were not appropriately coded in the current study.

Moving forward, a large prospective study that includes comorbidities would be helpful, but overall the study helps validate that “nipple-sparing mastectomy is a safe operation for selected patients,” Dr. Hwang said. 

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