Sharon Worcester

Adding oxaliplatin to fluoropyrimidine improves survival outcomes in patients with stage 3 N1 colon cancer whose tumors show microsatellite instability (MSI), according to a pooled analysis of individual patient data from 12 adjuvant trials.

The findings suggest the treatment combination should be the standard of care adjuvant treatment in this setting, and that N stage “should at least be a stratification parameter” in future trials in the MSI population, the investigators said.

Overall survival (OS) in 185 patients with MSI, which is associated with a deficient DNA mismatch repair system (dMMR), and 1,440 patients with microsatellite stability (MSS), which is associated with a proficient mismatch repair (pMMR), was better with the combination therapy versus fluoropyrimidine alone (adjusted hazard ratios, 0.52 and 0.89 for the groups, respectively), Romain Cohen, MD, PhD, of Saint-Antoine Hospital, medical oncology department, Sorbonne Universite, both in Paris, and colleagues reported online in the Journal of Clinical Oncology.
 

Encouraging results

Disease-free survival (DFS) was similarly improved with the combination therapy in the MSI and MSS groups (aHRs, 0.47 and 0.82, respectively).

Further, in 461 MSI/dMMR and 3,789 MSS/pMMR patients treated with the combination therapy, MSI status had different prognostic effects depending on N stage category.

“Compared with MSS/pMMR, MSI/dMMR was associated with better OS in the N1 population (HR, 0.66) but a similar OS in the N2 population (HR, 1.13),” they wrote.

Multivariate analysis showed that prognosticators for OS were N stage (HR for OS in N2 vs. N1, 3.10), T stage (HR for OS with T4 vs. T1-3, 2.39), and sex (HR for OS in men vs. women, HR, 1.71).

The 3-year DFS estimates for N2 vs. N1 disease in the MSI/dMMR group were 65% versus 87%, for T4 versus T1-3 they were 60.4% versus 82.1%, and for high- versus low-risk MSI/dMMR colorectal cancer patients they were 64.5% versus 90.1%.

“MSI/dMMR has become a major theranostic biomarker, harboring a high discrimination capacity for the efficacy of immune checkpoint inhibitors among patients with colorectal cancer,” the authors noted. “Given their impressive activity in the metastatic setting, this justifies evaluating these antibodies in the adjuvant setting.”

To date, the efficacy of the adding oxaliplatin to fluoropyrimidine inpatients with stage 3 colon cancer and MSI has not been clearly demonstrated, they added.

Therefore, they analyzed individual patient data from 12 randomized, controlled, phase 3 trials in the ACCENT database and adjusted for demographic and clinicopathologic factors.

“Here, in the T4 and/or N2 MSI/dMMR groups, we were able to identify populations of patients with MSI/dMMR [stage 3 colorectal cancer] with a high risk of disease recurrence. Indeed, the estimated 3-year DFS rates of patients with MSI/dMMR T4 stage III and N2 patients were, respectively, 60.4% and 64.9%, the latter experiencing poorer survival than the MSS/pMMR N2 population,” they wrote, concluding that, “with one-third of T4 and/or N2 high-risk ... patients experiencing disease recurrence or death within 2 years after curative tumor resection, therapeutic innovations should be sought for this patient population.”

This study was supported by the National Cancer Institute, the ARCAD foundation, and research grants from Nuovo-Soldati Foundation, ARC Foundation for Cancer Research, and Servier Institute. Dr. Cohen reported research funding and/or honoraria from Servier and MSD Oncology.

[email protected]

Adding oxaliplatin to fluoropyrimidine improves survival outcomes in patients with stage 3 N1 colon cancer whose tumors show microsatellite instability (MSI), according to a pooled analysis of individual patient data from 12 adjuvant trials.

The findings suggest the treatment combination should be the standard of care adjuvant treatment in this setting, and that N stage “should at least be a stratification parameter” in future trials in the MSI population, the investigators said.

Overall survival (OS) in 185 patients with MSI, which is associated with a deficient DNA mismatch repair system (dMMR), and 1,440 patients with microsatellite stability (MSS), which is associated with a proficient mismatch repair (pMMR), was better with the combination therapy versus fluoropyrimidine alone (adjusted hazard ratios, 0.52 and 0.89 for the groups, respectively), Romain Cohen, MD, PhD, of Saint-Antoine Hospital, medical oncology department, Sorbonne Universite, both in Paris, and colleagues reported online in the Journal of Clinical Oncology.
 

Encouraging results

Disease-free survival (DFS) was similarly improved with the combination therapy in the MSI and MSS groups (aHRs, 0.47 and 0.82, respectively).

Further, in 461 MSI/dMMR and 3,789 MSS/pMMR patients treated with the combination therapy, MSI status had different prognostic effects depending on N stage category.

“Compared with MSS/pMMR, MSI/dMMR was associated with better OS in the N1 population (HR, 0.66) but a similar OS in the N2 population (HR, 1.13),” they wrote.

Multivariate analysis showed that prognosticators for OS were N stage (HR for OS in N2 vs. N1, 3.10), T stage (HR for OS with T4 vs. T1-3, 2.39), and sex (HR for OS in men vs. women, HR, 1.71).

The 3-year DFS estimates for N2 vs. N1 disease in the MSI/dMMR group were 65% versus 87%, for T4 versus T1-3 they were 60.4% versus 82.1%, and for high- versus low-risk MSI/dMMR colorectal cancer patients they were 64.5% versus 90.1%.

“MSI/dMMR has become a major theranostic biomarker, harboring a high discrimination capacity for the efficacy of immune checkpoint inhibitors among patients with colorectal cancer,” the authors noted. “Given their impressive activity in the metastatic setting, this justifies evaluating these antibodies in the adjuvant setting.”

To date, the efficacy of the adding oxaliplatin to fluoropyrimidine inpatients with stage 3 colon cancer and MSI has not been clearly demonstrated, they added.

Therefore, they analyzed individual patient data from 12 randomized, controlled, phase 3 trials in the ACCENT database and adjusted for demographic and clinicopathologic factors.

“Here, in the T4 and/or N2 MSI/dMMR groups, we were able to identify populations of patients with MSI/dMMR [stage 3 colorectal cancer] with a high risk of disease recurrence. Indeed, the estimated 3-year DFS rates of patients with MSI/dMMR T4 stage III and N2 patients were, respectively, 60.4% and 64.9%, the latter experiencing poorer survival than the MSS/pMMR N2 population,” they wrote, concluding that, “with one-third of T4 and/or N2 high-risk ... patients experiencing disease recurrence or death within 2 years after curative tumor resection, therapeutic innovations should be sought for this patient population.”

This study was supported by the National Cancer Institute, the ARCAD foundation, and research grants from Nuovo-Soldati Foundation, ARC Foundation for Cancer Research, and Servier Institute. Dr. Cohen reported research funding and/or honoraria from Servier and MSD Oncology.

[email protected]

Adding oxaliplatin to fluoropyrimidine improves survival outcomes in patients with stage 3 N1 colon cancer whose tumors show microsatellite instability (MSI), according to a pooled analysis of individual patient data from 12 adjuvant trials.

The findings suggest the treatment combination should be the standard of care adjuvant treatment in this setting, and that N stage “should at least be a stratification parameter” in future trials in the MSI population, the investigators said.

Overall survival (OS) in 185 patients with MSI, which is associated with a deficient DNA mismatch repair system (dMMR), and 1,440 patients with microsatellite stability (MSS), which is associated with a proficient mismatch repair (pMMR), was better with the combination therapy versus fluoropyrimidine alone (adjusted hazard ratios, 0.52 and 0.89 for the groups, respectively), Romain Cohen, MD, PhD, of Saint-Antoine Hospital, medical oncology department, Sorbonne Universite, both in Paris, and colleagues reported online in the Journal of Clinical Oncology.
 

Encouraging results

Disease-free survival (DFS) was similarly improved with the combination therapy in the MSI and MSS groups (aHRs, 0.47 and 0.82, respectively).

Further, in 461 MSI/dMMR and 3,789 MSS/pMMR patients treated with the combination therapy, MSI status had different prognostic effects depending on N stage category.

“Compared with MSS/pMMR, MSI/dMMR was associated with better OS in the N1 population (HR, 0.66) but a similar OS in the N2 population (HR, 1.13),” they wrote.

Multivariate analysis showed that prognosticators for OS were N stage (HR for OS in N2 vs. N1, 3.10), T stage (HR for OS with T4 vs. T1-3, 2.39), and sex (HR for OS in men vs. women, HR, 1.71).

The 3-year DFS estimates for N2 vs. N1 disease in the MSI/dMMR group were 65% versus 87%, for T4 versus T1-3 they were 60.4% versus 82.1%, and for high- versus low-risk MSI/dMMR colorectal cancer patients they were 64.5% versus 90.1%.

“MSI/dMMR has become a major theranostic biomarker, harboring a high discrimination capacity for the efficacy of immune checkpoint inhibitors among patients with colorectal cancer,” the authors noted. “Given their impressive activity in the metastatic setting, this justifies evaluating these antibodies in the adjuvant setting.”

To date, the efficacy of the adding oxaliplatin to fluoropyrimidine inpatients with stage 3 colon cancer and MSI has not been clearly demonstrated, they added.

Therefore, they analyzed individual patient data from 12 randomized, controlled, phase 3 trials in the ACCENT database and adjusted for demographic and clinicopathologic factors.

“Here, in the T4 and/or N2 MSI/dMMR groups, we were able to identify populations of patients with MSI/dMMR [stage 3 colorectal cancer] with a high risk of disease recurrence. Indeed, the estimated 3-year DFS rates of patients with MSI/dMMR T4 stage III and N2 patients were, respectively, 60.4% and 64.9%, the latter experiencing poorer survival than the MSS/pMMR N2 population,” they wrote, concluding that, “with one-third of T4 and/or N2 high-risk ... patients experiencing disease recurrence or death within 2 years after curative tumor resection, therapeutic innovations should be sought for this patient population.”

This study was supported by the National Cancer Institute, the ARCAD foundation, and research grants from Nuovo-Soldati Foundation, ARC Foundation for Cancer Research, and Servier Institute. Dr. Cohen reported research funding and/or honoraria from Servier and MSD Oncology.

[email protected]

Among individuals who have received a hematopoietic stem cell transplant (HSCT), often used in the treatment of blood cancers, rates of survival are poor for those who develop COVID-19.

The probability of survival 30 days after being diagnosed with COVID-19 is only 68% for persons who have received an allogeneic HSCT and 67% for autologous HSCT recipients, according to new data from the Center for International Blood and Marrow Transplant Research.

These findings underscore the need for “stringent surveillance and aggressive treatment measures” in this population, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital, Memphis, and colleagues wrote.

The findings were published online March 1, 2021, in The Lancet Haematology.

The study is “of importance for physicians caring for HSCT recipients worldwide,” Mathieu Leclerc, MD, and Sébastien Maury, MD, Hôpital Henri Mondor, Créteil, France, commented in an accompanying editorial.
 

Study details

For their study, Dr. Sharma and colleagues analyzed outcomes for all HSCT recipients who developed COVID-19 and whose cases were reported to the CIBMTR. Of 318 such patients, 184 had undergone allogeneic HSCT, and 134 had undergone autologous HSCT.

Overall, about half of these patients (49%) had mild COVID-19.

Severe COVID-19 that required mechanical ventilation developed in 15% and 13% of the allogeneic and autologous HSCT recipients, respectively.

About one-fifth of patients died: 22% and 19% of allogeneic and autologous HSCT recipients, respectively.

Factors associated with greater mortality risk included age of 50 years or older (hazard ratio, 2.53), male sex (HR, 3.53), and development of COVID-19 within 12 months of undergoing HSCT (HR, 2.67).

Among autologous HSCT recipients, lymphoma was associated with higher mortality risk in comparison with a plasma cell disorder or myeloma (HR, 2.41), the authors noted.

“Two important messages can be drawn from the results reported by Sharma and colleagues,” Dr. Leclerc and Dr. Maury wrote in their editorial. “The first is the confirmation that the prognosis of COVID-19 is particularly poor in HSCT recipients, and that its prevention, in the absence of any specific curative treatment with sufficient efficacy, should be at the forefront of concerns.”

The second relates to the risk factors for death among HSCT recipients who develop COVID-19. In addition to previously known risk factors, such as age and gender, the investigators identified transplant-specific factors potentially associated with prognosis – namely, the nearly threefold increase in death among allogeneic HSCT recipients who develop COVID-19 within 12 months of transplant, they explained.

However, the findings are limited by a substantial amount of missing data, short follow-up, and the possibility of selection bias, they noted.

“Further large and well-designed studies with longer follow-up are needed to confirm and refine the results,” the editorialists wrote.

“[A] better understanding of the distinctive features of COVID-19 infection in HSCT recipients will be a necessary and essential step toward improvement of the remarkably poor prognosis observed in this setting,” they added.

The study was funded by the American Society of Hematology; the Leukemia and Lymphoma Society; the National Cancer Institute; the National Heart, Lung and Blood Institute; the National Institute of Allergy and Infectious Diseases; the National Institutes of Health; the Health Resources and Services Administration; and the Office of Naval Research. Dr. Sharma receives support for the conduct of industry-sponsored trials from Vertex Pharmaceuticals, CRISPR Therapeutics, and Novartis and consulting fees from Spotlight Therapeutics. Dr. Leclerc and Dr. Maury disclosed no relevant financial relationships.

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

Among individuals who have received a hematopoietic stem cell transplant (HSCT), often used in the treatment of blood cancers, rates of survival are poor for those who develop COVID-19.

The probability of survival 30 days after being diagnosed with COVID-19 is only 68% for persons who have received an allogeneic HSCT and 67% for autologous HSCT recipients, according to new data from the Center for International Blood and Marrow Transplant Research.

These findings underscore the need for “stringent surveillance and aggressive treatment measures” in this population, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital, Memphis, and colleagues wrote.

The findings were published online March 1, 2021, in The Lancet Haematology.

The study is “of importance for physicians caring for HSCT recipients worldwide,” Mathieu Leclerc, MD, and Sébastien Maury, MD, Hôpital Henri Mondor, Créteil, France, commented in an accompanying editorial.
 

Study details

For their study, Dr. Sharma and colleagues analyzed outcomes for all HSCT recipients who developed COVID-19 and whose cases were reported to the CIBMTR. Of 318 such patients, 184 had undergone allogeneic HSCT, and 134 had undergone autologous HSCT.

Overall, about half of these patients (49%) had mild COVID-19.

Severe COVID-19 that required mechanical ventilation developed in 15% and 13% of the allogeneic and autologous HSCT recipients, respectively.

About one-fifth of patients died: 22% and 19% of allogeneic and autologous HSCT recipients, respectively.

Factors associated with greater mortality risk included age of 50 years or older (hazard ratio, 2.53), male sex (HR, 3.53), and development of COVID-19 within 12 months of undergoing HSCT (HR, 2.67).

Among autologous HSCT recipients, lymphoma was associated with higher mortality risk in comparison with a plasma cell disorder or myeloma (HR, 2.41), the authors noted.

“Two important messages can be drawn from the results reported by Sharma and colleagues,” Dr. Leclerc and Dr. Maury wrote in their editorial. “The first is the confirmation that the prognosis of COVID-19 is particularly poor in HSCT recipients, and that its prevention, in the absence of any specific curative treatment with sufficient efficacy, should be at the forefront of concerns.”

The second relates to the risk factors for death among HSCT recipients who develop COVID-19. In addition to previously known risk factors, such as age and gender, the investigators identified transplant-specific factors potentially associated with prognosis – namely, the nearly threefold increase in death among allogeneic HSCT recipients who develop COVID-19 within 12 months of transplant, they explained.

However, the findings are limited by a substantial amount of missing data, short follow-up, and the possibility of selection bias, they noted.

“Further large and well-designed studies with longer follow-up are needed to confirm and refine the results,” the editorialists wrote.

“[A] better understanding of the distinctive features of COVID-19 infection in HSCT recipients will be a necessary and essential step toward improvement of the remarkably poor prognosis observed in this setting,” they added.

The study was funded by the American Society of Hematology; the Leukemia and Lymphoma Society; the National Cancer Institute; the National Heart, Lung and Blood Institute; the National Institute of Allergy and Infectious Diseases; the National Institutes of Health; the Health Resources and Services Administration; and the Office of Naval Research. Dr. Sharma receives support for the conduct of industry-sponsored trials from Vertex Pharmaceuticals, CRISPR Therapeutics, and Novartis and consulting fees from Spotlight Therapeutics. Dr. Leclerc and Dr. Maury disclosed no relevant financial relationships.

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

Among individuals who have received a hematopoietic stem cell transplant (HSCT), often used in the treatment of blood cancers, rates of survival are poor for those who develop COVID-19.

The probability of survival 30 days after being diagnosed with COVID-19 is only 68% for persons who have received an allogeneic HSCT and 67% for autologous HSCT recipients, according to new data from the Center for International Blood and Marrow Transplant Research.

These findings underscore the need for “stringent surveillance and aggressive treatment measures” in this population, Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital, Memphis, and colleagues wrote.

The findings were published online March 1, 2021, in The Lancet Haematology.

The study is “of importance for physicians caring for HSCT recipients worldwide,” Mathieu Leclerc, MD, and Sébastien Maury, MD, Hôpital Henri Mondor, Créteil, France, commented in an accompanying editorial.
 

Study details

For their study, Dr. Sharma and colleagues analyzed outcomes for all HSCT recipients who developed COVID-19 and whose cases were reported to the CIBMTR. Of 318 such patients, 184 had undergone allogeneic HSCT, and 134 had undergone autologous HSCT.

Overall, about half of these patients (49%) had mild COVID-19.

Severe COVID-19 that required mechanical ventilation developed in 15% and 13% of the allogeneic and autologous HSCT recipients, respectively.

About one-fifth of patients died: 22% and 19% of allogeneic and autologous HSCT recipients, respectively.

Factors associated with greater mortality risk included age of 50 years or older (hazard ratio, 2.53), male sex (HR, 3.53), and development of COVID-19 within 12 months of undergoing HSCT (HR, 2.67).

Among autologous HSCT recipients, lymphoma was associated with higher mortality risk in comparison with a plasma cell disorder or myeloma (HR, 2.41), the authors noted.

“Two important messages can be drawn from the results reported by Sharma and colleagues,” Dr. Leclerc and Dr. Maury wrote in their editorial. “The first is the confirmation that the prognosis of COVID-19 is particularly poor in HSCT recipients, and that its prevention, in the absence of any specific curative treatment with sufficient efficacy, should be at the forefront of concerns.”

The second relates to the risk factors for death among HSCT recipients who develop COVID-19. In addition to previously known risk factors, such as age and gender, the investigators identified transplant-specific factors potentially associated with prognosis – namely, the nearly threefold increase in death among allogeneic HSCT recipients who develop COVID-19 within 12 months of transplant, they explained.

However, the findings are limited by a substantial amount of missing data, short follow-up, and the possibility of selection bias, they noted.

“Further large and well-designed studies with longer follow-up are needed to confirm and refine the results,” the editorialists wrote.

“[A] better understanding of the distinctive features of COVID-19 infection in HSCT recipients will be a necessary and essential step toward improvement of the remarkably poor prognosis observed in this setting,” they added.

The study was funded by the American Society of Hematology; the Leukemia and Lymphoma Society; the National Cancer Institute; the National Heart, Lung and Blood Institute; the National Institute of Allergy and Infectious Diseases; the National Institutes of Health; the Health Resources and Services Administration; and the Office of Naval Research. Dr. Sharma receives support for the conduct of industry-sponsored trials from Vertex Pharmaceuticals, CRISPR Therapeutics, and Novartis and consulting fees from Spotlight Therapeutics. Dr. Leclerc and Dr. Maury disclosed no relevant financial relationships.

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

Women with gynecologic cancers can safely continue anticancer therapy, despite the threat of COVID-19, according to researchers.

The team found no significant association between recent anticancer therapy and COVID-19 hospitalization or mortality among patients with gynecologic cancers and COVID-19.

Some gynecologic cancer patients have expressed concerns that chemotherapy would weaken their immune system and increase their risk of more severe illness if they developed COVID-19, according to Olivia Lara, MD, a gynecologic oncology fellow at New York University.

Furthermore, some prior studies had shown an increased risk of health complications from COVID-19 among cancer patients. However, patients with gynecologic cancer were underrepresented in those studies.

With all this in mind, Dr. Lara and colleagues conducted a study of 193 patients with gynecologic cancers and COVID-19 who were treated at eight hospital systems in the New York City area from March 2020 through May 2020.

Dr. Lara presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10663).
 

Study results

Of the 193 patients analyzed, 106 (54.9%) required hospitalization for COVID-19, including 13 (12.3%) who required mechanical ventilation and 39 (36.8%) who required ICU admission. There were 34 patients (17.6%) who died of COVID-19-related complications, including all who required mechanical ventilation.

Multivariable analyses showed that recent cytotoxic chemotherapy, which was used in 13 of the 34 patients who died (38.2%), and recent immunotherapy, which was used in 4 of the 34 patients (11.8%), were not predictive of COVID-19 hospitalization or mortality.

Only current or former smoking was associated with COVID-19-related death (odds ratio, 2.75).

An earlier analysis of data from 121 patients in this cohort showed an association between immunotherapy and COVID-19-related death, but this was no longer statistically significant in the updated analysis.

Factors significantly associated with hospitalization in the updated cohort were age 65 years or older (OR, 2.12), Black race (OR, 2.53), performance status of 2 or greater (OR, 3.67), and the presence of three or more comorbidities (OR, 2.00), the most common of which were hypertension, diabetes, and chronic kidney disease.
 

More research needed

The current findings show that recent chemotherapy or immunotherapy for gynecologic cancer do not raise the risk of death due to COVID-19, Dr. Lara said, adding that “[w]e can reassure women with gynecologic cancer that they can continue anticancer therapy.”

The finding of a nearly threefold increased risk of hospitalization among Black patients in this study underscores the need for “better understanding of the risks of COVID-19 in vulnerable populations,” Dr. Lara noted.

“Going forward, the impact of the COVID-19 pandemic on cancer care delivery and cancer screening must be evaluated,” she said. “Data collection is ongoing, with additional analyses and studies planned to investigate the impact COVID-19 has had on gynecologic cancer care through the SGO registry.”

The current findings are strengthened by the collaborative multicenter study design and use of multivariable analyses, said invited discussant and study coauthor Bhavana Pothuri, MD, of New York University.

However, it is unclear whether the results are generalizable to other parts of the country or world, and whether the outcomes have changed since the initial surge of COVID-19 cases.

Dr. Lara said the fatality rate in this cohort is similar to that of age-matched women with COVID-19 who did not have cancer, and she acknowledged that fatality rates may be lower now than they were early in the pandemic when the study was conducted.

This study was supported, in part, by a Cancer Center Support Grant from the National Institutes of Health/National Cancer Institute. Dr. Lara reported having no disclosures. Dr. Pothuri disclosed relationships with Tesaro/GlaxoSmithKline, AstraZeneca, Merck, Genentech/Roche, Celsion, Clovis Oncology, Toray, Mersana, Elevar, and Eisai. She is also a member of GOG Partners leadership.

[email protected]

Women with gynecologic cancers can safely continue anticancer therapy, despite the threat of COVID-19, according to researchers.

The team found no significant association between recent anticancer therapy and COVID-19 hospitalization or mortality among patients with gynecologic cancers and COVID-19.

Some gynecologic cancer patients have expressed concerns that chemotherapy would weaken their immune system and increase their risk of more severe illness if they developed COVID-19, according to Olivia Lara, MD, a gynecologic oncology fellow at New York University.

Furthermore, some prior studies had shown an increased risk of health complications from COVID-19 among cancer patients. However, patients with gynecologic cancer were underrepresented in those studies.

With all this in mind, Dr. Lara and colleagues conducted a study of 193 patients with gynecologic cancers and COVID-19 who were treated at eight hospital systems in the New York City area from March 2020 through May 2020.

Dr. Lara presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10663).
 

Study results

Of the 193 patients analyzed, 106 (54.9%) required hospitalization for COVID-19, including 13 (12.3%) who required mechanical ventilation and 39 (36.8%) who required ICU admission. There were 34 patients (17.6%) who died of COVID-19-related complications, including all who required mechanical ventilation.

Multivariable analyses showed that recent cytotoxic chemotherapy, which was used in 13 of the 34 patients who died (38.2%), and recent immunotherapy, which was used in 4 of the 34 patients (11.8%), were not predictive of COVID-19 hospitalization or mortality.

Only current or former smoking was associated with COVID-19-related death (odds ratio, 2.75).

An earlier analysis of data from 121 patients in this cohort showed an association between immunotherapy and COVID-19-related death, but this was no longer statistically significant in the updated analysis.

Factors significantly associated with hospitalization in the updated cohort were age 65 years or older (OR, 2.12), Black race (OR, 2.53), performance status of 2 or greater (OR, 3.67), and the presence of three or more comorbidities (OR, 2.00), the most common of which were hypertension, diabetes, and chronic kidney disease.
 

More research needed

The current findings show that recent chemotherapy or immunotherapy for gynecologic cancer do not raise the risk of death due to COVID-19, Dr. Lara said, adding that “[w]e can reassure women with gynecologic cancer that they can continue anticancer therapy.”

The finding of a nearly threefold increased risk of hospitalization among Black patients in this study underscores the need for “better understanding of the risks of COVID-19 in vulnerable populations,” Dr. Lara noted.

“Going forward, the impact of the COVID-19 pandemic on cancer care delivery and cancer screening must be evaluated,” she said. “Data collection is ongoing, with additional analyses and studies planned to investigate the impact COVID-19 has had on gynecologic cancer care through the SGO registry.”

The current findings are strengthened by the collaborative multicenter study design and use of multivariable analyses, said invited discussant and study coauthor Bhavana Pothuri, MD, of New York University.

However, it is unclear whether the results are generalizable to other parts of the country or world, and whether the outcomes have changed since the initial surge of COVID-19 cases.

Dr. Lara said the fatality rate in this cohort is similar to that of age-matched women with COVID-19 who did not have cancer, and she acknowledged that fatality rates may be lower now than they were early in the pandemic when the study was conducted.

This study was supported, in part, by a Cancer Center Support Grant from the National Institutes of Health/National Cancer Institute. Dr. Lara reported having no disclosures. Dr. Pothuri disclosed relationships with Tesaro/GlaxoSmithKline, AstraZeneca, Merck, Genentech/Roche, Celsion, Clovis Oncology, Toray, Mersana, Elevar, and Eisai. She is also a member of GOG Partners leadership.

[email protected]

Women with gynecologic cancers can safely continue anticancer therapy, despite the threat of COVID-19, according to researchers.

The team found no significant association between recent anticancer therapy and COVID-19 hospitalization or mortality among patients with gynecologic cancers and COVID-19.

Some gynecologic cancer patients have expressed concerns that chemotherapy would weaken their immune system and increase their risk of more severe illness if they developed COVID-19, according to Olivia Lara, MD, a gynecologic oncology fellow at New York University.

Furthermore, some prior studies had shown an increased risk of health complications from COVID-19 among cancer patients. However, patients with gynecologic cancer were underrepresented in those studies.

With all this in mind, Dr. Lara and colleagues conducted a study of 193 patients with gynecologic cancers and COVID-19 who were treated at eight hospital systems in the New York City area from March 2020 through May 2020.

Dr. Lara presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10663).
 

Study results

Of the 193 patients analyzed, 106 (54.9%) required hospitalization for COVID-19, including 13 (12.3%) who required mechanical ventilation and 39 (36.8%) who required ICU admission. There were 34 patients (17.6%) who died of COVID-19-related complications, including all who required mechanical ventilation.

Multivariable analyses showed that recent cytotoxic chemotherapy, which was used in 13 of the 34 patients who died (38.2%), and recent immunotherapy, which was used in 4 of the 34 patients (11.8%), were not predictive of COVID-19 hospitalization or mortality.

Only current or former smoking was associated with COVID-19-related death (odds ratio, 2.75).

An earlier analysis of data from 121 patients in this cohort showed an association between immunotherapy and COVID-19-related death, but this was no longer statistically significant in the updated analysis.

Factors significantly associated with hospitalization in the updated cohort were age 65 years or older (OR, 2.12), Black race (OR, 2.53), performance status of 2 or greater (OR, 3.67), and the presence of three or more comorbidities (OR, 2.00), the most common of which were hypertension, diabetes, and chronic kidney disease.
 

More research needed

The current findings show that recent chemotherapy or immunotherapy for gynecologic cancer do not raise the risk of death due to COVID-19, Dr. Lara said, adding that “[w]e can reassure women with gynecologic cancer that they can continue anticancer therapy.”

The finding of a nearly threefold increased risk of hospitalization among Black patients in this study underscores the need for “better understanding of the risks of COVID-19 in vulnerable populations,” Dr. Lara noted.

“Going forward, the impact of the COVID-19 pandemic on cancer care delivery and cancer screening must be evaluated,” she said. “Data collection is ongoing, with additional analyses and studies planned to investigate the impact COVID-19 has had on gynecologic cancer care through the SGO registry.”

The current findings are strengthened by the collaborative multicenter study design and use of multivariable analyses, said invited discussant and study coauthor Bhavana Pothuri, MD, of New York University.

However, it is unclear whether the results are generalizable to other parts of the country or world, and whether the outcomes have changed since the initial surge of COVID-19 cases.

Dr. Lara said the fatality rate in this cohort is similar to that of age-matched women with COVID-19 who did not have cancer, and she acknowledged that fatality rates may be lower now than they were early in the pandemic when the study was conducted.

This study was supported, in part, by a Cancer Center Support Grant from the National Institutes of Health/National Cancer Institute. Dr. Lara reported having no disclosures. Dr. Pothuri disclosed relationships with Tesaro/GlaxoSmithKline, AstraZeneca, Merck, Genentech/Roche, Celsion, Clovis Oncology, Toray, Mersana, Elevar, and Eisai. She is also a member of GOG Partners leadership.

[email protected]

A clinical trial navigation program improved outcomes of Black women with endometrial cancer treated at a cancer center in the Deep South, according to researchers.

The team found that progression-free survival (PFS) was significantly worse for Black versus White women with endometrial cancer who were treated at the center between 2012 and 2018. However, PFS outcomes were similar for both races among patients from the center who were enrolled in clinical trials during the same period, after the center introduced a navigation program designed to reduce racial disparities.

The findings demonstrate that health care inequities can be overcome with specific interventions aimed at improving care for Black women, said Nathaniel L. Jones, MD of the Mitchell Cancer Institute at the University of South Alabama in Mobile.

Dr. Jones presented the findings at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10910).
 

Rationale: Building trust, providing equitable care

Black women comprise 7% of endometrial cancer diagnoses across the United States but account for 15% of all deaths, Dr. Jones noted. Compared with White women, Black women are up to 80% more likely to die from endometrial cancer.

“Perhaps even more concerning is that endometrial cancer is one of few cancers with increasing incidence and mortality, which further exacerbates the disparities,” Dr. Jones said.

In the Deep South, which carries “an unequal burden” of endometrial cancer incidence and mortality compared with the rest of the United States, multiple additional barriers exist that further exacerbate health care inequities, Dr. Jones said.

The barriers include greater poverty, mortality, social and economic disadvantages, and mistrust in “the medical establishment” among Black patients.

“The onus is on us as providers to provide an approach to cancer care that allows our patients to trust us and provide equitable cancer care for the women we serve,” Dr. Jones said. “To that end, we sought to investigate clinical trial enrollment at our institution after the implementation of patient-based programs designed specifically to enhance minority enrollment in clinical trials. We then evaluated the impact of clinical trial enrollment and race on survival.”
 

A ‘multifaceted’ intervention

“An intentional, multifaceted intervention was created to address Black patient enrollment onto clinical trials,” Dr. Jones explained.

His center implemented a lay navigation program to increase trial awareness and participation among minorities, help patients understand the risks and benefits of clinical trial participation, and help patients and their families navigate the enrollment and participation processes.

Under the program, all new endometrial cancer patients were assigned a lay navigator. The program included an education component to inform patients of the risks and benefits of clinical trial participation.

Another aspect was hiring a “diverse lay navigation workforce ... that mirrored the demographics of our catchment area,” which has more than double the minority population, compared with the national average, Dr. Jones noted.
 

Results: Improved PFS

To evaluate the efficacy of their intervention, the researchers conducted a retrospective review of 1,021 patients with endometrial cancer treated at Mitchell Cancer Institute between 2012 and 2018. There were 277 Black women and 718 White women in the overall cohort, and 23 Black women and 61 White women were enrolled in clinical trials.

After accounting for age-adjusted endometrial cancer incidence in the United States, the observed trial enrollment of Black women was statistically similar to expected enrollment (1.03-fold lower than expected). Compared with regional “Deep South” data, however, enrollment was 1.15-fold higher than expected for Black patients, Dr. Jones said.

Among all women with endometrial cancer treated at the Mitchell Cancer Institute, the median PFS was 14 months in Black women and 20 months in White women (P = .002). Among patients enrolled in clinical trials, however, the median PFS was 13 months for Black women and 14 months for White women (P = .280).

In the entire cohort, Black women had more aggressive histology, more advanced-stage disease, and a higher proportion of Medicaid or self-pay status. Among those enrolled in clinical trials, there was no difference between races in stage, grade, histology, insurance, or performance status.

The findings show that inequities in clinical trial enrollment can be overcome, and patient-based interventions can be helpful in improving enrollment of minority women, Dr. Jones concluded.
 

Doing better, starting small

Invited discussant Kemi M. Doll, MD, commended Dr. Jones and his colleagues for their “incredible, intervention-focused work,” but she asked: “Is this good enough?”

Analyses are needed to understand what drove the differences among trial participants versus the overall population, said Dr. Doll, a gynecologic oncologist at the University of Washington in Seattle.

For example, determining whether outcomes in the trial participants were driven by better PFS among Black women or worse PFS among White women could “help to identify next steps,” Dr. Doll said.

She stressed that “everyone” can engage in local-level efforts to improve trial enrollment, equity, and outcomes.

“A powerful mantra I was exposed to several years ago regarding equity is, ‘Here. Now. Small. Doable.’ We are often paralyzed by the long-standing and deeply embedded inequities in our health care system, but we can choose to move into action by following ‘Here. Now. Small. Doable,’” Dr. Doll said. “It reminds us to start where we are..., to start now, and stop waiting for convenience because equity work is not convenient.”

The key is recognizing individual power to enact change and focusing on “what we can change and not what we can’t,” she said.

Tools are available on the national level to help facilitate clinical trial enrollment of historically excluded populations, Dr. Doll added.

She cited a report outlining strategies for accruing diverse populations in clinical trials at eight U.S. cancer centers. The report addresses development of community partnerships and community advisory boards, training in culturally competent and congruent trial design, use of lay navigation, the importance of balancing benefits of participation with patient time and risk, and invoking a sense of altruism for family and community, Dr. Doll said.

“Baking these into trial design and recruitment are known, evidence-based methods to improve enrollment of [minority] populations,” she said. “Deciding to make these design elements mandatory for trials to be approved and executed is the kind of paradigm-shifting action that is available to us now.”

Dr. Jones and Dr. Doll both reported having no disclosures.

[email protected]

A clinical trial navigation program improved outcomes of Black women with endometrial cancer treated at a cancer center in the Deep South, according to researchers.

The team found that progression-free survival (PFS) was significantly worse for Black versus White women with endometrial cancer who were treated at the center between 2012 and 2018. However, PFS outcomes were similar for both races among patients from the center who were enrolled in clinical trials during the same period, after the center introduced a navigation program designed to reduce racial disparities.

The findings demonstrate that health care inequities can be overcome with specific interventions aimed at improving care for Black women, said Nathaniel L. Jones, MD of the Mitchell Cancer Institute at the University of South Alabama in Mobile.

Dr. Jones presented the findings at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10910).
 

Rationale: Building trust, providing equitable care

Black women comprise 7% of endometrial cancer diagnoses across the United States but account for 15% of all deaths, Dr. Jones noted. Compared with White women, Black women are up to 80% more likely to die from endometrial cancer.

“Perhaps even more concerning is that endometrial cancer is one of few cancers with increasing incidence and mortality, which further exacerbates the disparities,” Dr. Jones said.

In the Deep South, which carries “an unequal burden” of endometrial cancer incidence and mortality compared with the rest of the United States, multiple additional barriers exist that further exacerbate health care inequities, Dr. Jones said.

The barriers include greater poverty, mortality, social and economic disadvantages, and mistrust in “the medical establishment” among Black patients.

“The onus is on us as providers to provide an approach to cancer care that allows our patients to trust us and provide equitable cancer care for the women we serve,” Dr. Jones said. “To that end, we sought to investigate clinical trial enrollment at our institution after the implementation of patient-based programs designed specifically to enhance minority enrollment in clinical trials. We then evaluated the impact of clinical trial enrollment and race on survival.”
 

A ‘multifaceted’ intervention

“An intentional, multifaceted intervention was created to address Black patient enrollment onto clinical trials,” Dr. Jones explained.

His center implemented a lay navigation program to increase trial awareness and participation among minorities, help patients understand the risks and benefits of clinical trial participation, and help patients and their families navigate the enrollment and participation processes.

Under the program, all new endometrial cancer patients were assigned a lay navigator. The program included an education component to inform patients of the risks and benefits of clinical trial participation.

Another aspect was hiring a “diverse lay navigation workforce ... that mirrored the demographics of our catchment area,” which has more than double the minority population, compared with the national average, Dr. Jones noted.
 

Results: Improved PFS

To evaluate the efficacy of their intervention, the researchers conducted a retrospective review of 1,021 patients with endometrial cancer treated at Mitchell Cancer Institute between 2012 and 2018. There were 277 Black women and 718 White women in the overall cohort, and 23 Black women and 61 White women were enrolled in clinical trials.

After accounting for age-adjusted endometrial cancer incidence in the United States, the observed trial enrollment of Black women was statistically similar to expected enrollment (1.03-fold lower than expected). Compared with regional “Deep South” data, however, enrollment was 1.15-fold higher than expected for Black patients, Dr. Jones said.

Among all women with endometrial cancer treated at the Mitchell Cancer Institute, the median PFS was 14 months in Black women and 20 months in White women (P = .002). Among patients enrolled in clinical trials, however, the median PFS was 13 months for Black women and 14 months for White women (P = .280).

In the entire cohort, Black women had more aggressive histology, more advanced-stage disease, and a higher proportion of Medicaid or self-pay status. Among those enrolled in clinical trials, there was no difference between races in stage, grade, histology, insurance, or performance status.

The findings show that inequities in clinical trial enrollment can be overcome, and patient-based interventions can be helpful in improving enrollment of minority women, Dr. Jones concluded.
 

Doing better, starting small

Invited discussant Kemi M. Doll, MD, commended Dr. Jones and his colleagues for their “incredible, intervention-focused work,” but she asked: “Is this good enough?”

Analyses are needed to understand what drove the differences among trial participants versus the overall population, said Dr. Doll, a gynecologic oncologist at the University of Washington in Seattle.

For example, determining whether outcomes in the trial participants were driven by better PFS among Black women or worse PFS among White women could “help to identify next steps,” Dr. Doll said.

She stressed that “everyone” can engage in local-level efforts to improve trial enrollment, equity, and outcomes.

“A powerful mantra I was exposed to several years ago regarding equity is, ‘Here. Now. Small. Doable.’ We are often paralyzed by the long-standing and deeply embedded inequities in our health care system, but we can choose to move into action by following ‘Here. Now. Small. Doable,’” Dr. Doll said. “It reminds us to start where we are..., to start now, and stop waiting for convenience because equity work is not convenient.”

The key is recognizing individual power to enact change and focusing on “what we can change and not what we can’t,” she said.

Tools are available on the national level to help facilitate clinical trial enrollment of historically excluded populations, Dr. Doll added.

She cited a report outlining strategies for accruing diverse populations in clinical trials at eight U.S. cancer centers. The report addresses development of community partnerships and community advisory boards, training in culturally competent and congruent trial design, use of lay navigation, the importance of balancing benefits of participation with patient time and risk, and invoking a sense of altruism for family and community, Dr. Doll said.

“Baking these into trial design and recruitment are known, evidence-based methods to improve enrollment of [minority] populations,” she said. “Deciding to make these design elements mandatory for trials to be approved and executed is the kind of paradigm-shifting action that is available to us now.”

Dr. Jones and Dr. Doll both reported having no disclosures.

[email protected]

A clinical trial navigation program improved outcomes of Black women with endometrial cancer treated at a cancer center in the Deep South, according to researchers.

The team found that progression-free survival (PFS) was significantly worse for Black versus White women with endometrial cancer who were treated at the center between 2012 and 2018. However, PFS outcomes were similar for both races among patients from the center who were enrolled in clinical trials during the same period, after the center introduced a navigation program designed to reduce racial disparities.

The findings demonstrate that health care inequities can be overcome with specific interventions aimed at improving care for Black women, said Nathaniel L. Jones, MD of the Mitchell Cancer Institute at the University of South Alabama in Mobile.

Dr. Jones presented the findings at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10910).
 

Rationale: Building trust, providing equitable care

Black women comprise 7% of endometrial cancer diagnoses across the United States but account for 15% of all deaths, Dr. Jones noted. Compared with White women, Black women are up to 80% more likely to die from endometrial cancer.

“Perhaps even more concerning is that endometrial cancer is one of few cancers with increasing incidence and mortality, which further exacerbates the disparities,” Dr. Jones said.

In the Deep South, which carries “an unequal burden” of endometrial cancer incidence and mortality compared with the rest of the United States, multiple additional barriers exist that further exacerbate health care inequities, Dr. Jones said.

The barriers include greater poverty, mortality, social and economic disadvantages, and mistrust in “the medical establishment” among Black patients.

“The onus is on us as providers to provide an approach to cancer care that allows our patients to trust us and provide equitable cancer care for the women we serve,” Dr. Jones said. “To that end, we sought to investigate clinical trial enrollment at our institution after the implementation of patient-based programs designed specifically to enhance minority enrollment in clinical trials. We then evaluated the impact of clinical trial enrollment and race on survival.”
 

A ‘multifaceted’ intervention

“An intentional, multifaceted intervention was created to address Black patient enrollment onto clinical trials,” Dr. Jones explained.

His center implemented a lay navigation program to increase trial awareness and participation among minorities, help patients understand the risks and benefits of clinical trial participation, and help patients and their families navigate the enrollment and participation processes.

Under the program, all new endometrial cancer patients were assigned a lay navigator. The program included an education component to inform patients of the risks and benefits of clinical trial participation.

Another aspect was hiring a “diverse lay navigation workforce ... that mirrored the demographics of our catchment area,” which has more than double the minority population, compared with the national average, Dr. Jones noted.
 

Results: Improved PFS

To evaluate the efficacy of their intervention, the researchers conducted a retrospective review of 1,021 patients with endometrial cancer treated at Mitchell Cancer Institute between 2012 and 2018. There were 277 Black women and 718 White women in the overall cohort, and 23 Black women and 61 White women were enrolled in clinical trials.

After accounting for age-adjusted endometrial cancer incidence in the United States, the observed trial enrollment of Black women was statistically similar to expected enrollment (1.03-fold lower than expected). Compared with regional “Deep South” data, however, enrollment was 1.15-fold higher than expected for Black patients, Dr. Jones said.

Among all women with endometrial cancer treated at the Mitchell Cancer Institute, the median PFS was 14 months in Black women and 20 months in White women (P = .002). Among patients enrolled in clinical trials, however, the median PFS was 13 months for Black women and 14 months for White women (P = .280).

In the entire cohort, Black women had more aggressive histology, more advanced-stage disease, and a higher proportion of Medicaid or self-pay status. Among those enrolled in clinical trials, there was no difference between races in stage, grade, histology, insurance, or performance status.

The findings show that inequities in clinical trial enrollment can be overcome, and patient-based interventions can be helpful in improving enrollment of minority women, Dr. Jones concluded.
 

Doing better, starting small

Invited discussant Kemi M. Doll, MD, commended Dr. Jones and his colleagues for their “incredible, intervention-focused work,” but she asked: “Is this good enough?”

Analyses are needed to understand what drove the differences among trial participants versus the overall population, said Dr. Doll, a gynecologic oncologist at the University of Washington in Seattle.

For example, determining whether outcomes in the trial participants were driven by better PFS among Black women or worse PFS among White women could “help to identify next steps,” Dr. Doll said.

She stressed that “everyone” can engage in local-level efforts to improve trial enrollment, equity, and outcomes.

“A powerful mantra I was exposed to several years ago regarding equity is, ‘Here. Now. Small. Doable.’ We are often paralyzed by the long-standing and deeply embedded inequities in our health care system, but we can choose to move into action by following ‘Here. Now. Small. Doable,’” Dr. Doll said. “It reminds us to start where we are..., to start now, and stop waiting for convenience because equity work is not convenient.”

The key is recognizing individual power to enact change and focusing on “what we can change and not what we can’t,” she said.

Tools are available on the national level to help facilitate clinical trial enrollment of historically excluded populations, Dr. Doll added.

She cited a report outlining strategies for accruing diverse populations in clinical trials at eight U.S. cancer centers. The report addresses development of community partnerships and community advisory boards, training in culturally competent and congruent trial design, use of lay navigation, the importance of balancing benefits of participation with patient time and risk, and invoking a sense of altruism for family and community, Dr. Doll said.

“Baking these into trial design and recruitment are known, evidence-based methods to improve enrollment of [minority] populations,” she said. “Deciding to make these design elements mandatory for trials to be approved and executed is the kind of paradigm-shifting action that is available to us now.”

Dr. Jones and Dr. Doll both reported having no disclosures.

[email protected]

Adding andecaliximab (ADX) to first-line treatment with modified oxaliplatin, leucovorin, and fluorouracil (mFOLFOX6) provided no survival benefit in patients with advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma in the phase 3 GAMMA-1 study.

Objective response rates were 50.5% in the ADX arm and 41.1% in the placebo arm (stratified odds ratio, 1.47; P = .049), but this did not translate to improved survival.

The median overall survival (OS) was 12.5 months in the ADX arm and 11.8 months in the placebo arm (stratified hazard ratio, 0.93; P = .56). The median progression-free survival (PFS) was 7.5 months and 7.1 months, respectively (stratified HR, 0.84; P = .10).

Manish A. Shah, MD, of Weill Cornell Medicine, New York, and colleagues reported these results in the Journal of Clinical Oncology.

The lack of improvement when ADX was added to mFOLFOX6 was despite encouraging antitumor activity seen with the combination in a phase 1 and phase 1b study, the authors noted.

“Despite compelling early-phase data, the addition of ADX did not improve outcomes in an unselected patient population,” the authors wrote. “Tissue or blood samples were not available for correlative analyses to understand why ADX was less active than expected or to identify any gastric cancer subset that may derive greater benefit with ADX.”

The researchers did note, however, that subgroup analyses suggested survival benefits with ADX in patients aged 65 years and older.
 

Study details

Participants in the double-blind GAMMA-1 trial were adults with confirmed locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. They were enrolled at 132 centers worldwide between Oct. 13, 2015, and May 15, 2019.

There were 432 patients randomized to receive mFOLFOX6 plus either 800 mg of ADX (n = 218) or placebo (n = 214) infused on days 1 and 15 of each 28-day cycle until disease progression or intolerance.

As noted before, there was a significant improvement in response rate with the addition of ADX (P = .049) but no significant improvements in PFS (P = .10) or OS (P = .56).

On the other hand, subgroup analyses suggested survival benefits with ADX in patients aged 65 years and older. The authors said this result is intriguing and warrants further study.

Among patients aged 65 and older, the median OS was 13.9 months in the ADX arm and 10.5 months in the placebo arm (stratified HR, 0.64; P = .03). The median PFS was 8.7 months and 5.6 months, respectively (stratified HR, 0.50; P < .001). However, the P values were not adjusted for multiplicity.

No significant differences were seen between the groups with respect to safety outcomes. Serious adverse events occurred in 47.7% of patients in the ADX arm and 51.4% of those in the placebo arm. Nine patients in the ADX arm and 13 in the placebo arm discontinued the study because of adverse events.

The GAMMA-1 trial was sponsored by Gilead Sciences. The authors disclosed relationships with Gilead and many other companies.

[email protected]

Adding andecaliximab (ADX) to first-line treatment with modified oxaliplatin, leucovorin, and fluorouracil (mFOLFOX6) provided no survival benefit in patients with advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma in the phase 3 GAMMA-1 study.

Objective response rates were 50.5% in the ADX arm and 41.1% in the placebo arm (stratified odds ratio, 1.47; P = .049), but this did not translate to improved survival.

The median overall survival (OS) was 12.5 months in the ADX arm and 11.8 months in the placebo arm (stratified hazard ratio, 0.93; P = .56). The median progression-free survival (PFS) was 7.5 months and 7.1 months, respectively (stratified HR, 0.84; P = .10).

Manish A. Shah, MD, of Weill Cornell Medicine, New York, and colleagues reported these results in the Journal of Clinical Oncology.

The lack of improvement when ADX was added to mFOLFOX6 was despite encouraging antitumor activity seen with the combination in a phase 1 and phase 1b study, the authors noted.

“Despite compelling early-phase data, the addition of ADX did not improve outcomes in an unselected patient population,” the authors wrote. “Tissue or blood samples were not available for correlative analyses to understand why ADX was less active than expected or to identify any gastric cancer subset that may derive greater benefit with ADX.”

The researchers did note, however, that subgroup analyses suggested survival benefits with ADX in patients aged 65 years and older.
 

Study details

Participants in the double-blind GAMMA-1 trial were adults with confirmed locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. They were enrolled at 132 centers worldwide between Oct. 13, 2015, and May 15, 2019.

There were 432 patients randomized to receive mFOLFOX6 plus either 800 mg of ADX (n = 218) or placebo (n = 214) infused on days 1 and 15 of each 28-day cycle until disease progression or intolerance.

As noted before, there was a significant improvement in response rate with the addition of ADX (P = .049) but no significant improvements in PFS (P = .10) or OS (P = .56).

On the other hand, subgroup analyses suggested survival benefits with ADX in patients aged 65 years and older. The authors said this result is intriguing and warrants further study.

Among patients aged 65 and older, the median OS was 13.9 months in the ADX arm and 10.5 months in the placebo arm (stratified HR, 0.64; P = .03). The median PFS was 8.7 months and 5.6 months, respectively (stratified HR, 0.50; P < .001). However, the P values were not adjusted for multiplicity.

No significant differences were seen between the groups with respect to safety outcomes. Serious adverse events occurred in 47.7% of patients in the ADX arm and 51.4% of those in the placebo arm. Nine patients in the ADX arm and 13 in the placebo arm discontinued the study because of adverse events.

The GAMMA-1 trial was sponsored by Gilead Sciences. The authors disclosed relationships with Gilead and many other companies.

[email protected]

Adding andecaliximab (ADX) to first-line treatment with modified oxaliplatin, leucovorin, and fluorouracil (mFOLFOX6) provided no survival benefit in patients with advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma in the phase 3 GAMMA-1 study.

Objective response rates were 50.5% in the ADX arm and 41.1% in the placebo arm (stratified odds ratio, 1.47; P = .049), but this did not translate to improved survival.

The median overall survival (OS) was 12.5 months in the ADX arm and 11.8 months in the placebo arm (stratified hazard ratio, 0.93; P = .56). The median progression-free survival (PFS) was 7.5 months and 7.1 months, respectively (stratified HR, 0.84; P = .10).

Manish A. Shah, MD, of Weill Cornell Medicine, New York, and colleagues reported these results in the Journal of Clinical Oncology.

The lack of improvement when ADX was added to mFOLFOX6 was despite encouraging antitumor activity seen with the combination in a phase 1 and phase 1b study, the authors noted.

“Despite compelling early-phase data, the addition of ADX did not improve outcomes in an unselected patient population,” the authors wrote. “Tissue or blood samples were not available for correlative analyses to understand why ADX was less active than expected or to identify any gastric cancer subset that may derive greater benefit with ADX.”

The researchers did note, however, that subgroup analyses suggested survival benefits with ADX in patients aged 65 years and older.
 

Study details

Participants in the double-blind GAMMA-1 trial were adults with confirmed locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. They were enrolled at 132 centers worldwide between Oct. 13, 2015, and May 15, 2019.

There were 432 patients randomized to receive mFOLFOX6 plus either 800 mg of ADX (n = 218) or placebo (n = 214) infused on days 1 and 15 of each 28-day cycle until disease progression or intolerance.

As noted before, there was a significant improvement in response rate with the addition of ADX (P = .049) but no significant improvements in PFS (P = .10) or OS (P = .56).

On the other hand, subgroup analyses suggested survival benefits with ADX in patients aged 65 years and older. The authors said this result is intriguing and warrants further study.

Among patients aged 65 and older, the median OS was 13.9 months in the ADX arm and 10.5 months in the placebo arm (stratified HR, 0.64; P = .03). The median PFS was 8.7 months and 5.6 months, respectively (stratified HR, 0.50; P < .001). However, the P values were not adjusted for multiplicity.

No significant differences were seen between the groups with respect to safety outcomes. Serious adverse events occurred in 47.7% of patients in the ADX arm and 51.4% of those in the placebo arm. Nine patients in the ADX arm and 13 in the placebo arm discontinued the study because of adverse events.

The GAMMA-1 trial was sponsored by Gilead Sciences. The authors disclosed relationships with Gilead and many other companies.

[email protected]

In the United States, breast cancer mortality rates dropped every year for women across all age groups between 1989 and 2010, but after that, the trend stalled for those younger than 40 years.

“It’s clear that mortality rates in women under 40 are no longer decreasing,” lead author R. Edward Hendrick, PhD, clinical professor from the department of radiology at the University of Colorado at Denver, Aurora, stated in a press release. “I estimate that, in 2-3 years, the mortality rate will be increasing significantly in these women.”

These findings were published online Feb. 9, 2021, in Radiology.

The authors speculate that the findings may be related to recommendations for mammography screening.

For their study, the authors analyzed National Center for Health Statistics data for 1969-2017 and delay-adjusted invasive breast cancer incidence rates from the Surveillance, Epidemiology, and End Results program.

They found that breast cancer mortality rates decreased significantly by 1.5%-3.4% per year for all age groups from 1989 to 2010, and by 1.2%-2.2% per year after 2010 for those aged 40-79 years. However, the rates increased after 2010 by a nonsignificant 2.8% per year for women aged 20-29 years and 0.3% per year for those aged 30-39 years.

Distant-stage breast cancer incidence rates increased by more than 4% per year after the year 2000 in women aged 20-39 years.

“Our hope is that these findings focus more attention and research on breast cancer in younger women and what is behind this rapid increase in late-stage cancers,” Dr. Hendrick stated in the press release.

He and his colleagues speculate that the contrast between the upward trend in women aged younger than 40 years and the downward trend in older women highlights the value of mammography and may reflect the benefits of regular screening, which is not currently recommended for women younger than 40 who are not at high risk for breast cancer.

However, other groups, including the American College of Radiology and the Society for Breast Imaging, support starting annual mammograms at age 40 years.

An expert who was approached for comment noted that the incidence of breast cancer increases with age.

It is more common in women as they age, so screening recommendations do not include women aged younger than 40 years unless they are at very high risk for breast cancer, noted Joann G. Elmore, MD, MPH, professor of medicine at the University of California, Los Angeles.

“The majority of deaths due to breast cancer are in women over age 40. The breast cancer mortality rates per 100,000 as shown [in this study] are about 3 patients/100,000 for the under 40 age group, about 30/100,000 in the 40-69 age group, and about 80/100,000 in the 70 and above age group,” she pointed out.

Dr. Elmore was a coauthor of an editorial regarding the 2019 evidence-based guidance statement from the American College of Physicians . That guidance, which was endorsed by the U.S. Preventive Services Task Force, recommended screening every other year for average-risk women aged 50-74 years, as reported by this news organization.

In their editorial, Dr. Elmore and coauthor Christoph Lee, MD, of the University of Washington, Seattle, applauded the ACP’s approach but stressed that the guidance is not a perfect product and does not “clearly illuminate the full path ahead for every woman.”

Breast cancer screening guidelines continue to evolve, they said, concluding that “physicians are left to use their best judgment based on available research and expert recommendations.”

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

In the United States, breast cancer mortality rates dropped every year for women across all age groups between 1989 and 2010, but after that, the trend stalled for those younger than 40 years.

“It’s clear that mortality rates in women under 40 are no longer decreasing,” lead author R. Edward Hendrick, PhD, clinical professor from the department of radiology at the University of Colorado at Denver, Aurora, stated in a press release. “I estimate that, in 2-3 years, the mortality rate will be increasing significantly in these women.”

These findings were published online Feb. 9, 2021, in Radiology.

The authors speculate that the findings may be related to recommendations for mammography screening.

For their study, the authors analyzed National Center for Health Statistics data for 1969-2017 and delay-adjusted invasive breast cancer incidence rates from the Surveillance, Epidemiology, and End Results program.

They found that breast cancer mortality rates decreased significantly by 1.5%-3.4% per year for all age groups from 1989 to 2010, and by 1.2%-2.2% per year after 2010 for those aged 40-79 years. However, the rates increased after 2010 by a nonsignificant 2.8% per year for women aged 20-29 years and 0.3% per year for those aged 30-39 years.

Distant-stage breast cancer incidence rates increased by more than 4% per year after the year 2000 in women aged 20-39 years.

“Our hope is that these findings focus more attention and research on breast cancer in younger women and what is behind this rapid increase in late-stage cancers,” Dr. Hendrick stated in the press release.

He and his colleagues speculate that the contrast between the upward trend in women aged younger than 40 years and the downward trend in older women highlights the value of mammography and may reflect the benefits of regular screening, which is not currently recommended for women younger than 40 who are not at high risk for breast cancer.

However, other groups, including the American College of Radiology and the Society for Breast Imaging, support starting annual mammograms at age 40 years.

An expert who was approached for comment noted that the incidence of breast cancer increases with age.

It is more common in women as they age, so screening recommendations do not include women aged younger than 40 years unless they are at very high risk for breast cancer, noted Joann G. Elmore, MD, MPH, professor of medicine at the University of California, Los Angeles.

“The majority of deaths due to breast cancer are in women over age 40. The breast cancer mortality rates per 100,000 as shown [in this study] are about 3 patients/100,000 for the under 40 age group, about 30/100,000 in the 40-69 age group, and about 80/100,000 in the 70 and above age group,” she pointed out.

Dr. Elmore was a coauthor of an editorial regarding the 2019 evidence-based guidance statement from the American College of Physicians . That guidance, which was endorsed by the U.S. Preventive Services Task Force, recommended screening every other year for average-risk women aged 50-74 years, as reported by this news organization.

In their editorial, Dr. Elmore and coauthor Christoph Lee, MD, of the University of Washington, Seattle, applauded the ACP’s approach but stressed that the guidance is not a perfect product and does not “clearly illuminate the full path ahead for every woman.”

Breast cancer screening guidelines continue to evolve, they said, concluding that “physicians are left to use their best judgment based on available research and expert recommendations.”

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

In the United States, breast cancer mortality rates dropped every year for women across all age groups between 1989 and 2010, but after that, the trend stalled for those younger than 40 years.

“It’s clear that mortality rates in women under 40 are no longer decreasing,” lead author R. Edward Hendrick, PhD, clinical professor from the department of radiology at the University of Colorado at Denver, Aurora, stated in a press release. “I estimate that, in 2-3 years, the mortality rate will be increasing significantly in these women.”

These findings were published online Feb. 9, 2021, in Radiology.

The authors speculate that the findings may be related to recommendations for mammography screening.

For their study, the authors analyzed National Center for Health Statistics data for 1969-2017 and delay-adjusted invasive breast cancer incidence rates from the Surveillance, Epidemiology, and End Results program.

They found that breast cancer mortality rates decreased significantly by 1.5%-3.4% per year for all age groups from 1989 to 2010, and by 1.2%-2.2% per year after 2010 for those aged 40-79 years. However, the rates increased after 2010 by a nonsignificant 2.8% per year for women aged 20-29 years and 0.3% per year for those aged 30-39 years.

Distant-stage breast cancer incidence rates increased by more than 4% per year after the year 2000 in women aged 20-39 years.

“Our hope is that these findings focus more attention and research on breast cancer in younger women and what is behind this rapid increase in late-stage cancers,” Dr. Hendrick stated in the press release.

He and his colleagues speculate that the contrast between the upward trend in women aged younger than 40 years and the downward trend in older women highlights the value of mammography and may reflect the benefits of regular screening, which is not currently recommended for women younger than 40 who are not at high risk for breast cancer.

However, other groups, including the American College of Radiology and the Society for Breast Imaging, support starting annual mammograms at age 40 years.

An expert who was approached for comment noted that the incidence of breast cancer increases with age.

It is more common in women as they age, so screening recommendations do not include women aged younger than 40 years unless they are at very high risk for breast cancer, noted Joann G. Elmore, MD, MPH, professor of medicine at the University of California, Los Angeles.

“The majority of deaths due to breast cancer are in women over age 40. The breast cancer mortality rates per 100,000 as shown [in this study] are about 3 patients/100,000 for the under 40 age group, about 30/100,000 in the 40-69 age group, and about 80/100,000 in the 70 and above age group,” she pointed out.

Dr. Elmore was a coauthor of an editorial regarding the 2019 evidence-based guidance statement from the American College of Physicians . That guidance, which was endorsed by the U.S. Preventive Services Task Force, recommended screening every other year for average-risk women aged 50-74 years, as reported by this news organization.

In their editorial, Dr. Elmore and coauthor Christoph Lee, MD, of the University of Washington, Seattle, applauded the ACP’s approach but stressed that the guidance is not a perfect product and does not “clearly illuminate the full path ahead for every woman.”

Breast cancer screening guidelines continue to evolve, they said, concluding that “physicians are left to use their best judgment based on available research and expert recommendations.”

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

New guidelines from the American Society of Hematology “strongly recommend” using no thromboprophylaxis over using parenteral thromboprophylaxis in ambulatory patients receiving cancer chemotherapy who have low venous thromboembolism (VTE) risk, and using no thromboprophylaxis over oral thromboprophylaxis with vitamin K antagonists in those at any VTE risk level.

The evidence-based guidelines for the prevention and treatment of VTE in patient with cancer, published online in Blood Advances, also include a “conditional recommendation” for using either thromboprophylaxis with the direct oral anticoagulants (DOACs) apixaban or rivaroxaban or using no thromboprophylaxis in ambulatory patients with intermediate risk and using the DOACs over no thromboprophylaxis in those with high VTE risk.

The purpose of the guidelines, which also address VTE prophylaxis in hospitalized patients with cancer and the use of anticoagulation for VTE treatment in patients with cancer, is to provide clinical decision support for shared decision-making by patients and clinicians, Gary H. Lyman, MD, of Fred Hutchinson Cancer Research Center, Seattle and Marc Carrier, MD, of the University of Ottawa, and their colleagues from the multidisciplinary guidelines panel explained.

“The recommendations take into consideration the strength of the evidence, risks of mortality, VTE, and bleeding, as well as quality of life, acceptability, and cost considerations,” they wrote, noting that VTE is a common complication in patients with cancer, who are at markedly increased risk for morbidity and mortality from VTE.
 

Levels of evidence

The panel members relied on updated and original systematic evidence reviews. Conditional recommendations, as opposed to strong recommendations, are defined by the panel as “suggestions,” and all 33 recommendations that make up the guidelines include a statement on the strength of the relevant evidence.

For example, the thromboprophylaxis recommendations for low, intermediate, and high VTE risk are made based on “moderate certainty in the evidence of effects,” and the recommendation for no thromboprophylaxis over oral thromboprophylaxis with vitamin K antagonists is a strong recommendation based on “very low certainty in the evidence of benefits, but high certainty about the harms.”

The guidelines panel also strongly recommends, based on moderate certainty in the evidence of effects, using low-molecular-weight heparin over unfractionated heparin for the initial treatment of VTE in patients with cancer, and suggests, based on “very low certainty in the evidence of effects,” using LMWH over fondaparinux in this setting.

In addition to primary prophylaxis in ambulatory and hospitalized patients and initial VTE treatment, they also address primary prophylaxis for patients with cancer who have a central venous catheter, VTE treatment in surgical patients with cancer, short-term VTE treatment, and long-term VTE treatment.

For example, the guidelines panel conditionally recommends:

• Not using parenteral or oral thromboprophylaxis in patients with cancer and a central venous catheter
• Using LMWH or fondaparinux for surgical patients with cancer
• Using DOACS for the short-term treatment of VTE, and LMWH or DOACs for the long-term treatment of VTE in patients with cancer.

The perils of VTE

VTE in patients with cancer can interfere with treatment, increase mortality risk, and increase costs, the authors noted, adding that VTE can also adversely affect cancer patients’ quality of life.

“Some have even reported the experience of VTE to be more upsetting than that of the cancer,” they wrote. “More than 50% of thrombotic events occur within 3 months of the cancer diagnosis, a time when most cancer treatments will be underway. Patients, who are still coming to terms with a recent cancer diagnosis, often view the occurrence of VTE as a further threat to life, confirmation of the severity of their condition, and a poor prognostic sign.”

Therefore, the new guidelines aim to reduce VTE frequency, risk of bleeding complications, morbidity, and costs, thereby improving quality of life and the patient experience, the authors said, noting that three other recent guidelines on VTEs in patients with cancer have been published: the 2019 American Society of Clinical Oncology guidelines, the 2019 International Initiative on Thrombosis and Cancer guidelines, and the 2020 National Comprehensive Cancer Network guidelines.

The ASH guidelines are similar in many ways to the other guidelines, but differ in some ways, as well. An example is the timing of initiation of pharmacological thromboprophylaxis in patients undergoing cancer-related major abdominal surgery. The ASCO and ITAC guidelines advise starting thromboprophylaxis preoperatively, whereas the ASH guidelines recommend initiating thromboprophylaxis postoperatively, citing “the limited advantages to initiating thromboprophylaxis preoperatively, in addition to the potential bleeding and logistical considerations associated with neuraxial anesthesia.”

These differences highlight a lack of data in that setting and the need for additional studies, the authors said.
 

ASH vs. ASCO

James Douketis, MD, a practicing clinician and professor of medicine at McMaster University, Hamilton, Ont., highlighted another difference between the ASH and ASCO guidelines.

“For the treatment of [cancer-associated thrombosis], ASCO gives a strong recommendation to use LMWH or DOACs (with some caveats), which is easy to follow. ASH, on the other hand, suggests LMWH or a DOAC for the first 7-10 days, DOACs for the first 3-6 months, and back to LMWH or DOACs after 6 months,” he said in an interview.

The recommendation is “very evidence based but ambiguous and not helpful for the practicing clinician,” added Dr. Douketis, who helped develop the ITAC guidelines, but was not part of the ASH or ASCO guideline panels.

ASCO also provides a clear recommendation for giving VTE prophylaxis for 4 weeks after cancer surgery in patients with high VTE risk, whereas ASH gives “a somewhat vague recommendation” for thromboprophylaxis after hospital discharge.

The guidelines are “pretty well aligned” with respect to recommendations on VTE prophylaxis in medical cancer patients receiving chemotherapy, and although the “extremely academic” ASH guidelines were developed by “a superb team using the same evidence and excellent methodology,” they are interpreted in slightly different ways and fall short when it comes to being clinician friendly, Dr. Douketis said.

“At the end of day, for practicing clinicians, the ASH guidelines don’t provide a message that’s easy to digest,” he added.

ASH has, however, provided a resource page that includes tools and information for implementing the guidelines in clinical practice, and will maintain the guidelines “through surveillance for new evidence, ongoing review by experts, and regular revisions,” the authors said.

[email protected]

New guidelines from the American Society of Hematology “strongly recommend” using no thromboprophylaxis over using parenteral thromboprophylaxis in ambulatory patients receiving cancer chemotherapy who have low venous thromboembolism (VTE) risk, and using no thromboprophylaxis over oral thromboprophylaxis with vitamin K antagonists in those at any VTE risk level.

The evidence-based guidelines for the prevention and treatment of VTE in patient with cancer, published online in Blood Advances, also include a “conditional recommendation” for using either thromboprophylaxis with the direct oral anticoagulants (DOACs) apixaban or rivaroxaban or using no thromboprophylaxis in ambulatory patients with intermediate risk and using the DOACs over no thromboprophylaxis in those with high VTE risk.

The purpose of the guidelines, which also address VTE prophylaxis in hospitalized patients with cancer and the use of anticoagulation for VTE treatment in patients with cancer, is to provide clinical decision support for shared decision-making by patients and clinicians, Gary H. Lyman, MD, of Fred Hutchinson Cancer Research Center, Seattle and Marc Carrier, MD, of the University of Ottawa, and their colleagues from the multidisciplinary guidelines panel explained.

“The recommendations take into consideration the strength of the evidence, risks of mortality, VTE, and bleeding, as well as quality of life, acceptability, and cost considerations,” they wrote, noting that VTE is a common complication in patients with cancer, who are at markedly increased risk for morbidity and mortality from VTE.
 

Levels of evidence

The panel members relied on updated and original systematic evidence reviews. Conditional recommendations, as opposed to strong recommendations, are defined by the panel as “suggestions,” and all 33 recommendations that make up the guidelines include a statement on the strength of the relevant evidence.

For example, the thromboprophylaxis recommendations for low, intermediate, and high VTE risk are made based on “moderate certainty in the evidence of effects,” and the recommendation for no thromboprophylaxis over oral thromboprophylaxis with vitamin K antagonists is a strong recommendation based on “very low certainty in the evidence of benefits, but high certainty about the harms.”

The guidelines panel also strongly recommends, based on moderate certainty in the evidence of effects, using low-molecular-weight heparin over unfractionated heparin for the initial treatment of VTE in patients with cancer, and suggests, based on “very low certainty in the evidence of effects,” using LMWH over fondaparinux in this setting.

In addition to primary prophylaxis in ambulatory and hospitalized patients and initial VTE treatment, they also address primary prophylaxis for patients with cancer who have a central venous catheter, VTE treatment in surgical patients with cancer, short-term VTE treatment, and long-term VTE treatment.

For example, the guidelines panel conditionally recommends:

• Not using parenteral or oral thromboprophylaxis in patients with cancer and a central venous catheter
• Using LMWH or fondaparinux for surgical patients with cancer
• Using DOACS for the short-term treatment of VTE, and LMWH or DOACs for the long-term treatment of VTE in patients with cancer.

The perils of VTE

VTE in patients with cancer can interfere with treatment, increase mortality risk, and increase costs, the authors noted, adding that VTE can also adversely affect cancer patients’ quality of life.

“Some have even reported the experience of VTE to be more upsetting than that of the cancer,” they wrote. “More than 50% of thrombotic events occur within 3 months of the cancer diagnosis, a time when most cancer treatments will be underway. Patients, who are still coming to terms with a recent cancer diagnosis, often view the occurrence of VTE as a further threat to life, confirmation of the severity of their condition, and a poor prognostic sign.”

Therefore, the new guidelines aim to reduce VTE frequency, risk of bleeding complications, morbidity, and costs, thereby improving quality of life and the patient experience, the authors said, noting that three other recent guidelines on VTEs in patients with cancer have been published: the 2019 American Society of Clinical Oncology guidelines, the 2019 International Initiative on Thrombosis and Cancer guidelines, and the 2020 National Comprehensive Cancer Network guidelines.

The ASH guidelines are similar in many ways to the other guidelines, but differ in some ways, as well. An example is the timing of initiation of pharmacological thromboprophylaxis in patients undergoing cancer-related major abdominal surgery. The ASCO and ITAC guidelines advise starting thromboprophylaxis preoperatively, whereas the ASH guidelines recommend initiating thromboprophylaxis postoperatively, citing “the limited advantages to initiating thromboprophylaxis preoperatively, in addition to the potential bleeding and logistical considerations associated with neuraxial anesthesia.”

These differences highlight a lack of data in that setting and the need for additional studies, the authors said.
 

ASH vs. ASCO

James Douketis, MD, a practicing clinician and professor of medicine at McMaster University, Hamilton, Ont., highlighted another difference between the ASH and ASCO guidelines.

“For the treatment of [cancer-associated thrombosis], ASCO gives a strong recommendation to use LMWH or DOACs (with some caveats), which is easy to follow. ASH, on the other hand, suggests LMWH or a DOAC for the first 7-10 days, DOACs for the first 3-6 months, and back to LMWH or DOACs after 6 months,” he said in an interview.

The recommendation is “very evidence based but ambiguous and not helpful for the practicing clinician,” added Dr. Douketis, who helped develop the ITAC guidelines, but was not part of the ASH or ASCO guideline panels.

ASCO also provides a clear recommendation for giving VTE prophylaxis for 4 weeks after cancer surgery in patients with high VTE risk, whereas ASH gives “a somewhat vague recommendation” for thromboprophylaxis after hospital discharge.

The guidelines are “pretty well aligned” with respect to recommendations on VTE prophylaxis in medical cancer patients receiving chemotherapy, and although the “extremely academic” ASH guidelines were developed by “a superb team using the same evidence and excellent methodology,” they are interpreted in slightly different ways and fall short when it comes to being clinician friendly, Dr. Douketis said.

“At the end of day, for practicing clinicians, the ASH guidelines don’t provide a message that’s easy to digest,” he added.

ASH has, however, provided a resource page that includes tools and information for implementing the guidelines in clinical practice, and will maintain the guidelines “through surveillance for new evidence, ongoing review by experts, and regular revisions,” the authors said.

[email protected]

New guidelines from the American Society of Hematology “strongly recommend” using no thromboprophylaxis over using parenteral thromboprophylaxis in ambulatory patients receiving cancer chemotherapy who have low venous thromboembolism (VTE) risk, and using no thromboprophylaxis over oral thromboprophylaxis with vitamin K antagonists in those at any VTE risk level.

The evidence-based guidelines for the prevention and treatment of VTE in patient with cancer, published online in Blood Advances, also include a “conditional recommendation” for using either thromboprophylaxis with the direct oral anticoagulants (DOACs) apixaban or rivaroxaban or using no thromboprophylaxis in ambulatory patients with intermediate risk and using the DOACs over no thromboprophylaxis in those with high VTE risk.

The purpose of the guidelines, which also address VTE prophylaxis in hospitalized patients with cancer and the use of anticoagulation for VTE treatment in patients with cancer, is to provide clinical decision support for shared decision-making by patients and clinicians, Gary H. Lyman, MD, of Fred Hutchinson Cancer Research Center, Seattle and Marc Carrier, MD, of the University of Ottawa, and their colleagues from the multidisciplinary guidelines panel explained.

“The recommendations take into consideration the strength of the evidence, risks of mortality, VTE, and bleeding, as well as quality of life, acceptability, and cost considerations,” they wrote, noting that VTE is a common complication in patients with cancer, who are at markedly increased risk for morbidity and mortality from VTE.
 

Levels of evidence

The panel members relied on updated and original systematic evidence reviews. Conditional recommendations, as opposed to strong recommendations, are defined by the panel as “suggestions,” and all 33 recommendations that make up the guidelines include a statement on the strength of the relevant evidence.

For example, the thromboprophylaxis recommendations for low, intermediate, and high VTE risk are made based on “moderate certainty in the evidence of effects,” and the recommendation for no thromboprophylaxis over oral thromboprophylaxis with vitamin K antagonists is a strong recommendation based on “very low certainty in the evidence of benefits, but high certainty about the harms.”

The guidelines panel also strongly recommends, based on moderate certainty in the evidence of effects, using low-molecular-weight heparin over unfractionated heparin for the initial treatment of VTE in patients with cancer, and suggests, based on “very low certainty in the evidence of effects,” using LMWH over fondaparinux in this setting.

In addition to primary prophylaxis in ambulatory and hospitalized patients and initial VTE treatment, they also address primary prophylaxis for patients with cancer who have a central venous catheter, VTE treatment in surgical patients with cancer, short-term VTE treatment, and long-term VTE treatment.

For example, the guidelines panel conditionally recommends:

• Not using parenteral or oral thromboprophylaxis in patients with cancer and a central venous catheter
• Using LMWH or fondaparinux for surgical patients with cancer
• Using DOACS for the short-term treatment of VTE, and LMWH or DOACs for the long-term treatment of VTE in patients with cancer.

The perils of VTE

VTE in patients with cancer can interfere with treatment, increase mortality risk, and increase costs, the authors noted, adding that VTE can also adversely affect cancer patients’ quality of life.

“Some have even reported the experience of VTE to be more upsetting than that of the cancer,” they wrote. “More than 50% of thrombotic events occur within 3 months of the cancer diagnosis, a time when most cancer treatments will be underway. Patients, who are still coming to terms with a recent cancer diagnosis, often view the occurrence of VTE as a further threat to life, confirmation of the severity of their condition, and a poor prognostic sign.”

Therefore, the new guidelines aim to reduce VTE frequency, risk of bleeding complications, morbidity, and costs, thereby improving quality of life and the patient experience, the authors said, noting that three other recent guidelines on VTEs in patients with cancer have been published: the 2019 American Society of Clinical Oncology guidelines, the 2019 International Initiative on Thrombosis and Cancer guidelines, and the 2020 National Comprehensive Cancer Network guidelines.

The ASH guidelines are similar in many ways to the other guidelines, but differ in some ways, as well. An example is the timing of initiation of pharmacological thromboprophylaxis in patients undergoing cancer-related major abdominal surgery. The ASCO and ITAC guidelines advise starting thromboprophylaxis preoperatively, whereas the ASH guidelines recommend initiating thromboprophylaxis postoperatively, citing “the limited advantages to initiating thromboprophylaxis preoperatively, in addition to the potential bleeding and logistical considerations associated with neuraxial anesthesia.”

These differences highlight a lack of data in that setting and the need for additional studies, the authors said.
 

ASH vs. ASCO

James Douketis, MD, a practicing clinician and professor of medicine at McMaster University, Hamilton, Ont., highlighted another difference between the ASH and ASCO guidelines.

“For the treatment of [cancer-associated thrombosis], ASCO gives a strong recommendation to use LMWH or DOACs (with some caveats), which is easy to follow. ASH, on the other hand, suggests LMWH or a DOAC for the first 7-10 days, DOACs for the first 3-6 months, and back to LMWH or DOACs after 6 months,” he said in an interview.

The recommendation is “very evidence based but ambiguous and not helpful for the practicing clinician,” added Dr. Douketis, who helped develop the ITAC guidelines, but was not part of the ASH or ASCO guideline panels.

ASCO also provides a clear recommendation for giving VTE prophylaxis for 4 weeks after cancer surgery in patients with high VTE risk, whereas ASH gives “a somewhat vague recommendation” for thromboprophylaxis after hospital discharge.

The guidelines are “pretty well aligned” with respect to recommendations on VTE prophylaxis in medical cancer patients receiving chemotherapy, and although the “extremely academic” ASH guidelines were developed by “a superb team using the same evidence and excellent methodology,” they are interpreted in slightly different ways and fall short when it comes to being clinician friendly, Dr. Douketis said.

“At the end of day, for practicing clinicians, the ASH guidelines don’t provide a message that’s easy to digest,” he added.

ASH has, however, provided a resource page that includes tools and information for implementing the guidelines in clinical practice, and will maintain the guidelines “through surveillance for new evidence, ongoing review by experts, and regular revisions,” the authors said.

[email protected]

An integrated analysis of data derived from 99 treatment-naive glioblastomas has identified characteristics that could help stratify patients for more effective treatment, according to the investigators.

The analysis provides a detailed map of genes, proteins, infiltrating cells, and signaling pathways that play key roles in driving glioblastoma, Liang-Bo Wang, MD, of Washington University in St. Louis, and colleagues reported in Cancer Cell.

For example, the team identified key phosphorylation events as potential mediators of oncogenic pathway activation and potential targets for EGFR-, TP53-, and RB1-altered tumors. Specifically, phosphorylated PTPN11 and PLCG1 represent a signaling hub in RTK-altered tumors, they found.

The investigators also identified four immune glioblastoma tumor subtypes characterized by distinct immune cell populations. Type 1 tumors have a high macrophage count and few T cells, type 2 tumors have a moderate macrophage count, type 3 tumors have a high T-cell count and few macrophages, and type 4 tumors have few or no immune cells of any type.

They also found that mesenchymal subtype EMT signature is specific to tumor cells but not to stroma, and histone H2B acetylation is enriched in classical glioblastomas with low macrophage content.

“To improve therapies for this deadly cancer, understanding the tumor cells themselves is important but not enough,” senior author Li Ding, PhD, a professor of medicine and genetics and director of computational biology in the division of oncology at Washington University stated in a press release. “We also must understand the tumor cells’ interactions with the surrounding environment, including immune cells and the connective tissues and blood vessels.”

The investigators, including researchers from Pacific Northwest National Laboratory, Case Western Reserve University, and the National Cancer Institute, performed high-resolution and high-depth analyses on 99 tumors.

“Harnessing new technologies, including proteomics, metabolomics, and single-cell sequencing, this study is an extremely deep dive into glioblastoma tumor biology, revealing new possibilities for therapy,” Dr. Ding said.

The study, which is part of the NCI’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), is the largest and most detailed schematic of glioblastoma tumors to date, according to the press release.

The most immediate implication of the findings is better clinical trial design, study coauthor Milan G. Chheda, MD, stated in the press release.

Stratifying patients by tumor type, as identified in the current analysis, could allow researchers to test targeted therapies in the tumors most likely to respond to those therapies, explained Dr. Chheda, of Siteman Cancer Center at Barnes Jewish Hospital and Washington University.

The findings, particularly of multiple glioblastoma tumor subtypes, may explain the negative findings of trials looking at various immunotherapies for treating glioblastoma. Investigators for those trials haven’t considered the possibility of immune subgroups that may respond differently, the authors note, adding that research is underway to identify the best drugs to assess for the newly identified glioblastoma tumor types.

The study was supported by grants from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium, the National Human Genome Research Institute, and the National Institutes of Health.

Dr. Wang and Dr. Ding reported having no disclosures. Dr. Chheda receives research support from NeoimmuneTech and Orbus Therapeutics, and royalties from UpToDate.

[email protected]

An integrated analysis of data derived from 99 treatment-naive glioblastomas has identified characteristics that could help stratify patients for more effective treatment, according to the investigators.

The analysis provides a detailed map of genes, proteins, infiltrating cells, and signaling pathways that play key roles in driving glioblastoma, Liang-Bo Wang, MD, of Washington University in St. Louis, and colleagues reported in Cancer Cell.

For example, the team identified key phosphorylation events as potential mediators of oncogenic pathway activation and potential targets for EGFR-, TP53-, and RB1-altered tumors. Specifically, phosphorylated PTPN11 and PLCG1 represent a signaling hub in RTK-altered tumors, they found.

The investigators also identified four immune glioblastoma tumor subtypes characterized by distinct immune cell populations. Type 1 tumors have a high macrophage count and few T cells, type 2 tumors have a moderate macrophage count, type 3 tumors have a high T-cell count and few macrophages, and type 4 tumors have few or no immune cells of any type.

They also found that mesenchymal subtype EMT signature is specific to tumor cells but not to stroma, and histone H2B acetylation is enriched in classical glioblastomas with low macrophage content.

“To improve therapies for this deadly cancer, understanding the tumor cells themselves is important but not enough,” senior author Li Ding, PhD, a professor of medicine and genetics and director of computational biology in the division of oncology at Washington University stated in a press release. “We also must understand the tumor cells’ interactions with the surrounding environment, including immune cells and the connective tissues and blood vessels.”

The investigators, including researchers from Pacific Northwest National Laboratory, Case Western Reserve University, and the National Cancer Institute, performed high-resolution and high-depth analyses on 99 tumors.

“Harnessing new technologies, including proteomics, metabolomics, and single-cell sequencing, this study is an extremely deep dive into glioblastoma tumor biology, revealing new possibilities for therapy,” Dr. Ding said.

The study, which is part of the NCI’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), is the largest and most detailed schematic of glioblastoma tumors to date, according to the press release.

The most immediate implication of the findings is better clinical trial design, study coauthor Milan G. Chheda, MD, stated in the press release.

Stratifying patients by tumor type, as identified in the current analysis, could allow researchers to test targeted therapies in the tumors most likely to respond to those therapies, explained Dr. Chheda, of Siteman Cancer Center at Barnes Jewish Hospital and Washington University.

The findings, particularly of multiple glioblastoma tumor subtypes, may explain the negative findings of trials looking at various immunotherapies for treating glioblastoma. Investigators for those trials haven’t considered the possibility of immune subgroups that may respond differently, the authors note, adding that research is underway to identify the best drugs to assess for the newly identified glioblastoma tumor types.

The study was supported by grants from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium, the National Human Genome Research Institute, and the National Institutes of Health.

Dr. Wang and Dr. Ding reported having no disclosures. Dr. Chheda receives research support from NeoimmuneTech and Orbus Therapeutics, and royalties from UpToDate.

[email protected]

An integrated analysis of data derived from 99 treatment-naive glioblastomas has identified characteristics that could help stratify patients for more effective treatment, according to the investigators.

The analysis provides a detailed map of genes, proteins, infiltrating cells, and signaling pathways that play key roles in driving glioblastoma, Liang-Bo Wang, MD, of Washington University in St. Louis, and colleagues reported in Cancer Cell.

For example, the team identified key phosphorylation events as potential mediators of oncogenic pathway activation and potential targets for EGFR-, TP53-, and RB1-altered tumors. Specifically, phosphorylated PTPN11 and PLCG1 represent a signaling hub in RTK-altered tumors, they found.

The investigators also identified four immune glioblastoma tumor subtypes characterized by distinct immune cell populations. Type 1 tumors have a high macrophage count and few T cells, type 2 tumors have a moderate macrophage count, type 3 tumors have a high T-cell count and few macrophages, and type 4 tumors have few or no immune cells of any type.

They also found that mesenchymal subtype EMT signature is specific to tumor cells but not to stroma, and histone H2B acetylation is enriched in classical glioblastomas with low macrophage content.

“To improve therapies for this deadly cancer, understanding the tumor cells themselves is important but not enough,” senior author Li Ding, PhD, a professor of medicine and genetics and director of computational biology in the division of oncology at Washington University stated in a press release. “We also must understand the tumor cells’ interactions with the surrounding environment, including immune cells and the connective tissues and blood vessels.”

The investigators, including researchers from Pacific Northwest National Laboratory, Case Western Reserve University, and the National Cancer Institute, performed high-resolution and high-depth analyses on 99 tumors.

“Harnessing new technologies, including proteomics, metabolomics, and single-cell sequencing, this study is an extremely deep dive into glioblastoma tumor biology, revealing new possibilities for therapy,” Dr. Ding said.

The study, which is part of the NCI’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), is the largest and most detailed schematic of glioblastoma tumors to date, according to the press release.

The most immediate implication of the findings is better clinical trial design, study coauthor Milan G. Chheda, MD, stated in the press release.

Stratifying patients by tumor type, as identified in the current analysis, could allow researchers to test targeted therapies in the tumors most likely to respond to those therapies, explained Dr. Chheda, of Siteman Cancer Center at Barnes Jewish Hospital and Washington University.

The findings, particularly of multiple glioblastoma tumor subtypes, may explain the negative findings of trials looking at various immunotherapies for treating glioblastoma. Investigators for those trials haven’t considered the possibility of immune subgroups that may respond differently, the authors note, adding that research is underway to identify the best drugs to assess for the newly identified glioblastoma tumor types.

The study was supported by grants from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium, the National Human Genome Research Institute, and the National Institutes of Health.

Dr. Wang and Dr. Ding reported having no disclosures. Dr. Chheda receives research support from NeoimmuneTech and Orbus Therapeutics, and royalties from UpToDate.

[email protected]

Residual fixatives from liquid-based Pap tests and cervical swabs contain tumor-specific biomarkers for ovarian cancer, according to an analysis of proteins found in matched biospecimens from a woman with high grade serous ovarian cancer.

The findings suggest that Pap test fluid or cervical swabs could be used to detect ovarian cancer biomarker proteins to allow for earlier detection of ovarian cancer, reported Kristin L. M. Boylan, PhD, assistant director of the Ovarian Cancer Early Detection Program at the University of Minnesota, Minneapolis, and colleagues.

The investigators examined the biospecimens from a 72-year-old woman diagnosed with metastatic high-grade serous adenocarcinoma that did not encompass the cervix. The Pap test, obtained prior to surgery, was negative for malignancy, but nearly 5,000 proteins were detected in the three matched biospecimens, including more than 2,000 that were expressed in each of them.

These proteins included several known ovarian cancer biomarkers, such as CA125, HE4, and mesothelin, the investigators noted.

The findings were published online Feb. 9 in Clinical Proteomics.

“Our data demonstrate that ovarian cancer biomarkers can be detected in Pap test fluid or a cervical swab by MS-based proteomics,” the investigators wrote. “In addition to identifying multiple known biomarkers, over 2,000 proteins were detected in all three biospecimens, suggesting a potential role for novel biomarker discovery.”

Proteins from the cell-free supernatant of the patient’s liquid-based Pap test fixative were concentrated by acetone precipitation or eluted from the cervical swab, and protein was also extracted from the patient’s tumor. Analyses showed similarities in the Pap test fluid and cervical swab proteins, as well as the tumor extract.

The findings are notable, because while early detection of ovarian cancer increases survival, an adequately sensitive and specific screening tool for use in the general population is lacking, the investigators explained.

Pap test screening is widely accepted, suggesting that developing it as a screening tool for both cervical and ovarian cancers could improve testing for this “lethal but elusive disease,” they said, addding that “[W]hile our samples were from a single patient, the results are proof of concept: that Pap test fluid or cervical swabs could be used for detection of ovarian cancer biomarker proteins, and this approach warrants further investigation.”

Senior author Amy Skubitz, PhD, professor and director of the Ovarian Cancer Early Detection Program, stated in a press release that she “sees an opportunity for this method to be translated into a self-administered, at-home test, where swabs could be collected by women at home and sent to a central laboratory for analysis of proteins that would diagnose ovarian cancer.”

However, next steps include using quantitative mass spectrometry to determine if the proteins or peptides identified in this analysis are detected at higher levels in ovarian cancer Pap tests or swabs compared to controls.

“Their presence alone is not sufficient for diagnosis,” she stated.

This study was supported by the Minnesota Ovarian Cancer Alliance, the Cancurables Foundation, Charlene’s Light: A Foundation for Ovarian Cancer, and the Department of Defense Ovarian Cancer Research Program Pilot Award. The authors reported having no disclosures.

[email protected]

Residual fixatives from liquid-based Pap tests and cervical swabs contain tumor-specific biomarkers for ovarian cancer, according to an analysis of proteins found in matched biospecimens from a woman with high grade serous ovarian cancer.

The findings suggest that Pap test fluid or cervical swabs could be used to detect ovarian cancer biomarker proteins to allow for earlier detection of ovarian cancer, reported Kristin L. M. Boylan, PhD, assistant director of the Ovarian Cancer Early Detection Program at the University of Minnesota, Minneapolis, and colleagues.

The investigators examined the biospecimens from a 72-year-old woman diagnosed with metastatic high-grade serous adenocarcinoma that did not encompass the cervix. The Pap test, obtained prior to surgery, was negative for malignancy, but nearly 5,000 proteins were detected in the three matched biospecimens, including more than 2,000 that were expressed in each of them.

These proteins included several known ovarian cancer biomarkers, such as CA125, HE4, and mesothelin, the investigators noted.

The findings were published online Feb. 9 in Clinical Proteomics.

“Our data demonstrate that ovarian cancer biomarkers can be detected in Pap test fluid or a cervical swab by MS-based proteomics,” the investigators wrote. “In addition to identifying multiple known biomarkers, over 2,000 proteins were detected in all three biospecimens, suggesting a potential role for novel biomarker discovery.”

Proteins from the cell-free supernatant of the patient’s liquid-based Pap test fixative were concentrated by acetone precipitation or eluted from the cervical swab, and protein was also extracted from the patient’s tumor. Analyses showed similarities in the Pap test fluid and cervical swab proteins, as well as the tumor extract.

The findings are notable, because while early detection of ovarian cancer increases survival, an adequately sensitive and specific screening tool for use in the general population is lacking, the investigators explained.

Pap test screening is widely accepted, suggesting that developing it as a screening tool for both cervical and ovarian cancers could improve testing for this “lethal but elusive disease,” they said, addding that “[W]hile our samples were from a single patient, the results are proof of concept: that Pap test fluid or cervical swabs could be used for detection of ovarian cancer biomarker proteins, and this approach warrants further investigation.”

Senior author Amy Skubitz, PhD, professor and director of the Ovarian Cancer Early Detection Program, stated in a press release that she “sees an opportunity for this method to be translated into a self-administered, at-home test, where swabs could be collected by women at home and sent to a central laboratory for analysis of proteins that would diagnose ovarian cancer.”

However, next steps include using quantitative mass spectrometry to determine if the proteins or peptides identified in this analysis are detected at higher levels in ovarian cancer Pap tests or swabs compared to controls.

“Their presence alone is not sufficient for diagnosis,” she stated.

This study was supported by the Minnesota Ovarian Cancer Alliance, the Cancurables Foundation, Charlene’s Light: A Foundation for Ovarian Cancer, and the Department of Defense Ovarian Cancer Research Program Pilot Award. The authors reported having no disclosures.

[email protected]

Residual fixatives from liquid-based Pap tests and cervical swabs contain tumor-specific biomarkers for ovarian cancer, according to an analysis of proteins found in matched biospecimens from a woman with high grade serous ovarian cancer.

The findings suggest that Pap test fluid or cervical swabs could be used to detect ovarian cancer biomarker proteins to allow for earlier detection of ovarian cancer, reported Kristin L. M. Boylan, PhD, assistant director of the Ovarian Cancer Early Detection Program at the University of Minnesota, Minneapolis, and colleagues.

The investigators examined the biospecimens from a 72-year-old woman diagnosed with metastatic high-grade serous adenocarcinoma that did not encompass the cervix. The Pap test, obtained prior to surgery, was negative for malignancy, but nearly 5,000 proteins were detected in the three matched biospecimens, including more than 2,000 that were expressed in each of them.

These proteins included several known ovarian cancer biomarkers, such as CA125, HE4, and mesothelin, the investigators noted.

The findings were published online Feb. 9 in Clinical Proteomics.

“Our data demonstrate that ovarian cancer biomarkers can be detected in Pap test fluid or a cervical swab by MS-based proteomics,” the investigators wrote. “In addition to identifying multiple known biomarkers, over 2,000 proteins were detected in all three biospecimens, suggesting a potential role for novel biomarker discovery.”

Proteins from the cell-free supernatant of the patient’s liquid-based Pap test fixative were concentrated by acetone precipitation or eluted from the cervical swab, and protein was also extracted from the patient’s tumor. Analyses showed similarities in the Pap test fluid and cervical swab proteins, as well as the tumor extract.

The findings are notable, because while early detection of ovarian cancer increases survival, an adequately sensitive and specific screening tool for use in the general population is lacking, the investigators explained.

Pap test screening is widely accepted, suggesting that developing it as a screening tool for both cervical and ovarian cancers could improve testing for this “lethal but elusive disease,” they said, addding that “[W]hile our samples were from a single patient, the results are proof of concept: that Pap test fluid or cervical swabs could be used for detection of ovarian cancer biomarker proteins, and this approach warrants further investigation.”

Senior author Amy Skubitz, PhD, professor and director of the Ovarian Cancer Early Detection Program, stated in a press release that she “sees an opportunity for this method to be translated into a self-administered, at-home test, where swabs could be collected by women at home and sent to a central laboratory for analysis of proteins that would diagnose ovarian cancer.”

However, next steps include using quantitative mass spectrometry to determine if the proteins or peptides identified in this analysis are detected at higher levels in ovarian cancer Pap tests or swabs compared to controls.

“Their presence alone is not sufficient for diagnosis,” she stated.

This study was supported by the Minnesota Ovarian Cancer Alliance, the Cancurables Foundation, Charlene’s Light: A Foundation for Ovarian Cancer, and the Department of Defense Ovarian Cancer Research Program Pilot Award. The authors reported having no disclosures.

[email protected]

A novel quantitative assay used with flow cytometry helps to precisely measure chimeric antigen receptor (CAR) T-cell engraftment and in vivo expansion to predict patient outcomes after CAR T-cell infusion, according to researchers at the Fondazione IRCCS Istituto Nazionale Tumorion in Milan.

Higher frequencies of CAR-positive T cells at day 9 after infusion, as measured using the polymerase chain reaction (PCR)-based assay, accurately distinguished responders from nonresponders, Paolo Corradini, MD, said at the 3rd European CAR T-cell Meeting.

The findings, first presented in December at the American Society of Hematology annual conference, suggest the assay could improve treatment decision-making, Dr. Corradini of the University of Milan said at the meeting, which is jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association

He and his colleagues prospectively collected samples from 16 patients with diffuse large B-cell lymphoma, 5 with transformed follicular lymphoma, and 7 with primary mediastinal B-cell lymphoma who were treated with either axicabtagene ciloleucel (axi-cel; Yescarta) or tisagenlecleucel (tisa-cal; Kymriah) between November 2019 and July 2020. CAR T cells were monitored using flow cytometry.

Pivotal trial data and subsequent findings with respect to tisa-cel and axi-cel have demonstrated that CAR T-cell engraftment and in vivo expansion have a crucial impact on disease response and toxicity: a cut-off value of CAR+ cells at day 9 greater than 24.5/microliters distinguished responders from nonresponders with a sensitivity of 87.5% and specificity of 81%, Dr. Corradini noted.

“But we have also devised a methodology by digital droplet PCR (ddPCR) recently that correlates perfectly with the flow cytometry data,” he said, adding that the assay is “easy and allowed precise enumeration of the CAR T cells in the blood of the patient.”

The R square (coefficient of determination) for ddPCR and flow cytometry was 0.9995 and 0.9997 for tisa-cel and axi-cel, respectively (P < .0001 for each). This is particularly useful for assessing whether low CAR T-cell levels on flow cytometry are background signals resulting from nonspecific binding of the antibodies or true low levels, and the findings therefore have implications for improving clinical decision-making and outcomes in CAR T-cell therapy recipients, he said.

[email protected]

A novel quantitative assay used with flow cytometry helps to precisely measure chimeric antigen receptor (CAR) T-cell engraftment and in vivo expansion to predict patient outcomes after CAR T-cell infusion, according to researchers at the Fondazione IRCCS Istituto Nazionale Tumorion in Milan.

Higher frequencies of CAR-positive T cells at day 9 after infusion, as measured using the polymerase chain reaction (PCR)-based assay, accurately distinguished responders from nonresponders, Paolo Corradini, MD, said at the 3rd European CAR T-cell Meeting.

The findings, first presented in December at the American Society of Hematology annual conference, suggest the assay could improve treatment decision-making, Dr. Corradini of the University of Milan said at the meeting, which is jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association

He and his colleagues prospectively collected samples from 16 patients with diffuse large B-cell lymphoma, 5 with transformed follicular lymphoma, and 7 with primary mediastinal B-cell lymphoma who were treated with either axicabtagene ciloleucel (axi-cel; Yescarta) or tisagenlecleucel (tisa-cal; Kymriah) between November 2019 and July 2020. CAR T cells were monitored using flow cytometry.

Pivotal trial data and subsequent findings with respect to tisa-cel and axi-cel have demonstrated that CAR T-cell engraftment and in vivo expansion have a crucial impact on disease response and toxicity: a cut-off value of CAR+ cells at day 9 greater than 24.5/microliters distinguished responders from nonresponders with a sensitivity of 87.5% and specificity of 81%, Dr. Corradini noted.

“But we have also devised a methodology by digital droplet PCR (ddPCR) recently that correlates perfectly with the flow cytometry data,” he said, adding that the assay is “easy and allowed precise enumeration of the CAR T cells in the blood of the patient.”

The R square (coefficient of determination) for ddPCR and flow cytometry was 0.9995 and 0.9997 for tisa-cel and axi-cel, respectively (P < .0001 for each). This is particularly useful for assessing whether low CAR T-cell levels on flow cytometry are background signals resulting from nonspecific binding of the antibodies or true low levels, and the findings therefore have implications for improving clinical decision-making and outcomes in CAR T-cell therapy recipients, he said.

[email protected]

A novel quantitative assay used with flow cytometry helps to precisely measure chimeric antigen receptor (CAR) T-cell engraftment and in vivo expansion to predict patient outcomes after CAR T-cell infusion, according to researchers at the Fondazione IRCCS Istituto Nazionale Tumorion in Milan.

Higher frequencies of CAR-positive T cells at day 9 after infusion, as measured using the polymerase chain reaction (PCR)-based assay, accurately distinguished responders from nonresponders, Paolo Corradini, MD, said at the 3rd European CAR T-cell Meeting.

The findings, first presented in December at the American Society of Hematology annual conference, suggest the assay could improve treatment decision-making, Dr. Corradini of the University of Milan said at the meeting, which is jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association

He and his colleagues prospectively collected samples from 16 patients with diffuse large B-cell lymphoma, 5 with transformed follicular lymphoma, and 7 with primary mediastinal B-cell lymphoma who were treated with either axicabtagene ciloleucel (axi-cel; Yescarta) or tisagenlecleucel (tisa-cal; Kymriah) between November 2019 and July 2020. CAR T cells were monitored using flow cytometry.

Pivotal trial data and subsequent findings with respect to tisa-cel and axi-cel have demonstrated that CAR T-cell engraftment and in vivo expansion have a crucial impact on disease response and toxicity: a cut-off value of CAR+ cells at day 9 greater than 24.5/microliters distinguished responders from nonresponders with a sensitivity of 87.5% and specificity of 81%, Dr. Corradini noted.

“But we have also devised a methodology by digital droplet PCR (ddPCR) recently that correlates perfectly with the flow cytometry data,” he said, adding that the assay is “easy and allowed precise enumeration of the CAR T cells in the blood of the patient.”

The R square (coefficient of determination) for ddPCR and flow cytometry was 0.9995 and 0.9997 for tisa-cel and axi-cel, respectively (P < .0001 for each). This is particularly useful for assessing whether low CAR T-cell levels on flow cytometry are background signals resulting from nonspecific binding of the antibodies or true low levels, and the findings therefore have implications for improving clinical decision-making and outcomes in CAR T-cell therapy recipients, he said.

[email protected]