Lymphoma & Plasma Cell Disorders

In the 1970s, cancer survival was poor for young children and older adults in the United States, as shown by data published in the Journal of the National Cancer Institute.

Great progress has been made since the 1970s, but improvements in outcome have been less impressive for cancer patients aged 15-39 years, as shown by research published in Cancer.

Factors that contribute to the AYA gap

About 89,000 AYAs are diagnosed with cancer each year in the United States, according to data from the National Cancer Institute (NCI). Lymphomas and thyroid cancer are the most common cancers among younger AYAs, aged 15-24 years.

In a report commissioned by the NIH in 2006, many factors contributing to the AYA gap were identified. Chief among them were:

• Limitations in access to care.
• Delayed diagnosis.
• Inconsistency in treatment and follow-up.
• Long-term toxicity (fertility, second malignancies, and cardiovascular disease).

These factors compromise health-related survival, even when cancer-specific survival is improved.

Panelist Kara Kelly, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., noted that there are additional unique challenges for AYAs with cancer. These include:

• Pubertal changes.
• Developmental transition to independence.
• Societal impediments such as insurance coverage and disparities in access to specialized centers.
• Psychosocial factors such as health literacy and adherence to treatment and follow-up.

Focusing on lymphoma specifically, Dr. Kelly noted that lymphoma biology differs across the age spectrum and by race and ethnicity. Both tumor and host factors require further study, she said.
 

Clinical trial access for AYAs

Dr. Kelly emphasized that, unfortunately, clinical research participation is low among AYAs. A major impediment is that adult clinical trials historically required participants to be at least 18 years old.

In addition, there has not been a focused effort to educate AYAs about regulatory safeguards to ensure safety and the promise of enhanced benefit to them in NCI Cancer Trials Network (NCTN) trials. As a result, the refusal rate is high.

A multi-stakeholder workshop, convened in May 2016 by the American Society of Clinical Oncology and Friends of Cancer Research, outlined opportunities for expanding trial eligibility to include children younger than 18 years in first-in-human and other adult cancer clinical trials, enhancing their access to new agents, without compromising safety.

Recently, collaborative efforts between the adult and children’s NCTN research groups have included AYAs in studies addressing cancers that span the age spectrum, including lymphoma.

However, as Dr. Kelly noted, there are differences in AYA lymphoid malignancy types with a transition from more pediatric to more adult types.
 

Hodgkin lymphoma and primary mediastinal B-cell lymphoma

Panelist Lisa G. Roth, MD, of Weill Cornell Medicine, New York, reviewed the genomic landscape of Hodgkin lymphoma (HL) and primary mediastinal B-cell lymphoma (PMBCL).

Dr. Roth explained that both HL and PMBCL are derived from thymic B cells, predominantly affect the mediastinum, and are CD30-positive lymphomas. Both are characterized by upregulation of JAK/STAT and NF-kappaB as well as overexpression of PD-L1.

Dr. Roth noted that HL is challenging to sequence by standard methods because Reed Sternberg (HRS) cells represent less than 1% of the cellular infiltrate. Recurrently mutated genes in HL cluster by histologic subtype.

Whole-exome sequencing of HRS cells show loss of beta-2 microglobulin and MHC-1 expression, HLA-B, NF-kappaB signaling, and JAK-STAT signaling, according to data published in Blood Advances in 2019.

Dr. Roth’s lab performed immunohistochemistry on tissue microarrays in 145 cases of HL (unpublished data). Results showed that loss of beta-2 microglobulin is more common in younger HL patients. For other alterations, there were too few cases to know.

Dr. Roth’s lab is a member of a pediatric/AYA HL sequencing multi-institutional consortium that has been able to extract DNA and RNA from samples submitted for whole-exome sequencing. The consortium’s goal is to shed light on implications of other genomic alterations that may differ by age in HL patients.

Dr. Roth cited research showing that PMBCL shares molecular alterations similar to those of HL. Alterations in PMBCL suggest dysregulated cellular signaling and immune evasion mechanisms (e.g., deletions in MHC type 1 and 2, beta-2 microglobulin, JAK-STAT, and NF-kappaB mutations) that provide opportunities to study novel agents, according to data published in Blood in 2019.

By early 2021, the S1826 and ANHL1931 studies, which have no age restriction, will be available to AYA lymphoma patients with HL and PMBCL, respectively, Dr. Roth said.
 

Follicular lymphoma: Clinical features by age

Panelist Abner Louissaint Jr, MD, PhD, of Massachusetts General Hospital in Boston, discussed age-related differences in follicular lymphoma (FL).

He noted that FL typically presents at an advanced stage, with low- or high-grade histology. It is increasingly common in adults in their 50s and 60s, representing 20% of all lymphomas. FL is rare in children and AYAs.

Dr. Louissaint explained that the typical flow cytometric findings in FL are BCL2 translocations, occurring in up to 85%-90% of low-grade and 50% of high-grade cases. The t(14;18)(q32;q21) translocation juxtaposes BCL2 on 18q21 to regulatory sequences and enhances the expression of elements of the Ig heavy chain.

Malignant cells in FL patients express CD20, CD10, CD21, and BCL2 (in contrast to normal germinal centers) and overexpress BCL6 (in contrast to normal follicles), Dr. Louissaint noted. He said the Ki-67 proliferative index of the malignant cells is typically low.

Pediatric-type FL is rare, but case series show clinical, pathologic, and molecular features that are distinctive from adult FL, Dr. Louissaint explained.

He then discussed the features of pediatric-type FL in multiple domains. In the clinical domain, there is a male predilection, and stage tends to be low. There is frequent involvement of nodes of the head and neck region and rare involvement of internal lymph node chains.

Pathologically, the malignant cells appear high grade, with architectural effacement, expansile follicular pattern, large lymphocyte size, and an elevated proliferation index. In contrast to adult FL, malignant cells in pediatric-type FL lack aberrant BCL2 expression.

Most importantly, for pediatric-type FL, the prognosis is excellent with durable remissions after surgical excision, Dr. Louissaint said.
 

Follicular lymphoma: Molecular features by age

Because of the excellent prognosis in pediatric-type FL, it is important to assess whether young adults with FL have adult-type or pediatric-type lesions, Dr. Louissaint said.

He cited many studies showing differences in adult and pediatric-type FL. In adult FL, the mutational landscape is characterized by frequent chromatin-modifying mutations in genes such as CREBBP, KM22D, and EP300.

In contrast, in pediatric-type FL, there are frequent activating MAPK pathway mutations, including mutations in the negative regulatory domain of MAP2K1. These mutations are not seen in adult FL.

Dr. Louissaint noted that there may be mutations in epigenetic modifiers (CREBBP, TNFRSF14) in both adult and pediatric-type FL. However, CREBBP is very unusual in pediatric-type FL and common in adult FL. This suggests the alterations in pediatric-type FL do not simply represent an early stage of the same disease as adult FL.

Despite a high proliferating fraction and absence of BCL2/BCL6/IRF4 rearrangements in pediatric-type FL, the presence of these features was associated with dramatic difference in progression-free survival, according to research published in Blood in 2012.
 

A distinct entity

In 2016, the World Health Organization recognized pediatric-type FL as a distinct entity, with the following diagnostic criteria (published in Blood):

• At least partial effacement of nodal architecture, expansile follicles, intermediate-size blastoid cells, and no component of diffuse large B-cell lymphoma.
• Immunohistochemistry showing BCL6 positivity, BCL2 negativity or weak positivity, and a high proliferative fraction.
• Genomic studies showing no BCL2 amplification.
• Clinical features of nodal disease in the head and neck region, early clinical stage, age younger than 40 years, typically in a male with no internal nodes involved.

When FL occurs in AYAs, the diagnostic findings of pediatric-type FL suggest the patient will do well with conservative management (e.g., excision alone), Dr. Louissaint noted.
 

Two sizes do not fit all

The strategies that have improved cancer outcomes since the 1970s for children and older adults have been much less successful for AYAs with cancer.

As an oncologic community, we should not allow the AYA gap to persist. As always, the solutions are likely to involve focused clinical research, education, and communication. Effort will need to be targeted specifically to the AYA population.

Since health-related mortality is high even when cancer-specific outcomes improve, adopting and maintaining a healthy lifestyle must be a key part of the discussion with these young patients.

The biologic differences associated with AYA lymphomas demand participation in clinical trials.

Oncologists should vigorously support removing impediments to the participation of AYAs in prospective clinical trials, stratified (but unrestricted) by age, with careful analysis of patient-reported outcomes, late adverse effects, and biospecimen collection.

As Dr. Kelly noted in the question-and-answer period, the Children’s Oncology Group has an existing biobank of paraffin-embedded tumor samples, DNA from lymphoma specimens, plasma, and sera with clinically annotated data that can be given to investigators upon request and justification.
 

Going beyond eligibility for clinical trials

Unfortunately, we will likely find that broadening eligibility criteria is the “low-hanging fruit.” There are protocol-, patient-, and physician-related obstacles, according to a review published in Cancer in 2019.

Patient-related obstacles include fear of toxicity, uncertainty about placebos, a steep learning curve for health literacy, insurance-related impediments, and other access-related issues.

Discussions will need to be tailored to the AYA population. Frank, early conversations about fertility, sexuality, financial hardship, career advancement, work-life balance, and cognitive risks may not only facilitate treatment planning but also encourage the trust that is essential for patients to enroll in trials.

The investment in time, multidisciplinary staff and physician involvement, and potential delays in treatment initiation may be painful and inconvenient, but the benefits for long-term health outcomes and personal-professional relationships will be gratifying beyond measure.

Dr. Smith disclosed relationships with Genentech/Roche, Celgene, TGTX, Karyopharm, Janssen, and Bantem. Dr. Roth disclosed relationships with Janssen, ADC Therapeutics, and Celgene. Dr. Kelly and Dr. Louissaint had no financial relationships to disclose.



Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

In the 1970s, cancer survival was poor for young children and older adults in the United States, as shown by data published in the Journal of the National Cancer Institute.

Great progress has been made since the 1970s, but improvements in outcome have been less impressive for cancer patients aged 15-39 years, as shown by research published in Cancer.

Factors that contribute to the AYA gap

About 89,000 AYAs are diagnosed with cancer each year in the United States, according to data from the National Cancer Institute (NCI). Lymphomas and thyroid cancer are the most common cancers among younger AYAs, aged 15-24 years.

In a report commissioned by the NIH in 2006, many factors contributing to the AYA gap were identified. Chief among them were:

• Limitations in access to care.
• Delayed diagnosis.
• Inconsistency in treatment and follow-up.
• Long-term toxicity (fertility, second malignancies, and cardiovascular disease).

These factors compromise health-related survival, even when cancer-specific survival is improved.

Panelist Kara Kelly, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., noted that there are additional unique challenges for AYAs with cancer. These include:

• Pubertal changes.
• Developmental transition to independence.
• Societal impediments such as insurance coverage and disparities in access to specialized centers.
• Psychosocial factors such as health literacy and adherence to treatment and follow-up.

Focusing on lymphoma specifically, Dr. Kelly noted that lymphoma biology differs across the age spectrum and by race and ethnicity. Both tumor and host factors require further study, she said.
 

Clinical trial access for AYAs

Dr. Kelly emphasized that, unfortunately, clinical research participation is low among AYAs. A major impediment is that adult clinical trials historically required participants to be at least 18 years old.

In addition, there has not been a focused effort to educate AYAs about regulatory safeguards to ensure safety and the promise of enhanced benefit to them in NCI Cancer Trials Network (NCTN) trials. As a result, the refusal rate is high.

A multi-stakeholder workshop, convened in May 2016 by the American Society of Clinical Oncology and Friends of Cancer Research, outlined opportunities for expanding trial eligibility to include children younger than 18 years in first-in-human and other adult cancer clinical trials, enhancing their access to new agents, without compromising safety.

Recently, collaborative efforts between the adult and children’s NCTN research groups have included AYAs in studies addressing cancers that span the age spectrum, including lymphoma.

However, as Dr. Kelly noted, there are differences in AYA lymphoid malignancy types with a transition from more pediatric to more adult types.
 

Hodgkin lymphoma and primary mediastinal B-cell lymphoma

Panelist Lisa G. Roth, MD, of Weill Cornell Medicine, New York, reviewed the genomic landscape of Hodgkin lymphoma (HL) and primary mediastinal B-cell lymphoma (PMBCL).

Dr. Roth explained that both HL and PMBCL are derived from thymic B cells, predominantly affect the mediastinum, and are CD30-positive lymphomas. Both are characterized by upregulation of JAK/STAT and NF-kappaB as well as overexpression of PD-L1.

Dr. Roth noted that HL is challenging to sequence by standard methods because Reed Sternberg (HRS) cells represent less than 1% of the cellular infiltrate. Recurrently mutated genes in HL cluster by histologic subtype.

Whole-exome sequencing of HRS cells show loss of beta-2 microglobulin and MHC-1 expression, HLA-B, NF-kappaB signaling, and JAK-STAT signaling, according to data published in Blood Advances in 2019.

Dr. Roth’s lab performed immunohistochemistry on tissue microarrays in 145 cases of HL (unpublished data). Results showed that loss of beta-2 microglobulin is more common in younger HL patients. For other alterations, there were too few cases to know.

Dr. Roth’s lab is a member of a pediatric/AYA HL sequencing multi-institutional consortium that has been able to extract DNA and RNA from samples submitted for whole-exome sequencing. The consortium’s goal is to shed light on implications of other genomic alterations that may differ by age in HL patients.

Dr. Roth cited research showing that PMBCL shares molecular alterations similar to those of HL. Alterations in PMBCL suggest dysregulated cellular signaling and immune evasion mechanisms (e.g., deletions in MHC type 1 and 2, beta-2 microglobulin, JAK-STAT, and NF-kappaB mutations) that provide opportunities to study novel agents, according to data published in Blood in 2019.

By early 2021, the S1826 and ANHL1931 studies, which have no age restriction, will be available to AYA lymphoma patients with HL and PMBCL, respectively, Dr. Roth said.
 

Follicular lymphoma: Clinical features by age

Panelist Abner Louissaint Jr, MD, PhD, of Massachusetts General Hospital in Boston, discussed age-related differences in follicular lymphoma (FL).

He noted that FL typically presents at an advanced stage, with low- or high-grade histology. It is increasingly common in adults in their 50s and 60s, representing 20% of all lymphomas. FL is rare in children and AYAs.

Dr. Louissaint explained that the typical flow cytometric findings in FL are BCL2 translocations, occurring in up to 85%-90% of low-grade and 50% of high-grade cases. The t(14;18)(q32;q21) translocation juxtaposes BCL2 on 18q21 to regulatory sequences and enhances the expression of elements of the Ig heavy chain.

Malignant cells in FL patients express CD20, CD10, CD21, and BCL2 (in contrast to normal germinal centers) and overexpress BCL6 (in contrast to normal follicles), Dr. Louissaint noted. He said the Ki-67 proliferative index of the malignant cells is typically low.

Pediatric-type FL is rare, but case series show clinical, pathologic, and molecular features that are distinctive from adult FL, Dr. Louissaint explained.

He then discussed the features of pediatric-type FL in multiple domains. In the clinical domain, there is a male predilection, and stage tends to be low. There is frequent involvement of nodes of the head and neck region and rare involvement of internal lymph node chains.

Pathologically, the malignant cells appear high grade, with architectural effacement, expansile follicular pattern, large lymphocyte size, and an elevated proliferation index. In contrast to adult FL, malignant cells in pediatric-type FL lack aberrant BCL2 expression.

Most importantly, for pediatric-type FL, the prognosis is excellent with durable remissions after surgical excision, Dr. Louissaint said.
 

Follicular lymphoma: Molecular features by age

Because of the excellent prognosis in pediatric-type FL, it is important to assess whether young adults with FL have adult-type or pediatric-type lesions, Dr. Louissaint said.

He cited many studies showing differences in adult and pediatric-type FL. In adult FL, the mutational landscape is characterized by frequent chromatin-modifying mutations in genes such as CREBBP, KM22D, and EP300.

In contrast, in pediatric-type FL, there are frequent activating MAPK pathway mutations, including mutations in the negative regulatory domain of MAP2K1. These mutations are not seen in adult FL.

Dr. Louissaint noted that there may be mutations in epigenetic modifiers (CREBBP, TNFRSF14) in both adult and pediatric-type FL. However, CREBBP is very unusual in pediatric-type FL and common in adult FL. This suggests the alterations in pediatric-type FL do not simply represent an early stage of the same disease as adult FL.

Despite a high proliferating fraction and absence of BCL2/BCL6/IRF4 rearrangements in pediatric-type FL, the presence of these features was associated with dramatic difference in progression-free survival, according to research published in Blood in 2012.
 

A distinct entity

In 2016, the World Health Organization recognized pediatric-type FL as a distinct entity, with the following diagnostic criteria (published in Blood):

• At least partial effacement of nodal architecture, expansile follicles, intermediate-size blastoid cells, and no component of diffuse large B-cell lymphoma.
• Immunohistochemistry showing BCL6 positivity, BCL2 negativity or weak positivity, and a high proliferative fraction.
• Genomic studies showing no BCL2 amplification.
• Clinical features of nodal disease in the head and neck region, early clinical stage, age younger than 40 years, typically in a male with no internal nodes involved.

When FL occurs in AYAs, the diagnostic findings of pediatric-type FL suggest the patient will do well with conservative management (e.g., excision alone), Dr. Louissaint noted.
 

Two sizes do not fit all

The strategies that have improved cancer outcomes since the 1970s for children and older adults have been much less successful for AYAs with cancer.

As an oncologic community, we should not allow the AYA gap to persist. As always, the solutions are likely to involve focused clinical research, education, and communication. Effort will need to be targeted specifically to the AYA population.

Since health-related mortality is high even when cancer-specific outcomes improve, adopting and maintaining a healthy lifestyle must be a key part of the discussion with these young patients.

The biologic differences associated with AYA lymphomas demand participation in clinical trials.

Oncologists should vigorously support removing impediments to the participation of AYAs in prospective clinical trials, stratified (but unrestricted) by age, with careful analysis of patient-reported outcomes, late adverse effects, and biospecimen collection.

As Dr. Kelly noted in the question-and-answer period, the Children’s Oncology Group has an existing biobank of paraffin-embedded tumor samples, DNA from lymphoma specimens, plasma, and sera with clinically annotated data that can be given to investigators upon request and justification.
 

Going beyond eligibility for clinical trials

Unfortunately, we will likely find that broadening eligibility criteria is the “low-hanging fruit.” There are protocol-, patient-, and physician-related obstacles, according to a review published in Cancer in 2019.

Patient-related obstacles include fear of toxicity, uncertainty about placebos, a steep learning curve for health literacy, insurance-related impediments, and other access-related issues.

Discussions will need to be tailored to the AYA population. Frank, early conversations about fertility, sexuality, financial hardship, career advancement, work-life balance, and cognitive risks may not only facilitate treatment planning but also encourage the trust that is essential for patients to enroll in trials.

The investment in time, multidisciplinary staff and physician involvement, and potential delays in treatment initiation may be painful and inconvenient, but the benefits for long-term health outcomes and personal-professional relationships will be gratifying beyond measure.

Dr. Smith disclosed relationships with Genentech/Roche, Celgene, TGTX, Karyopharm, Janssen, and Bantem. Dr. Roth disclosed relationships with Janssen, ADC Therapeutics, and Celgene. Dr. Kelly and Dr. Louissaint had no financial relationships to disclose.



Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

In the 1970s, cancer survival was poor for young children and older adults in the United States, as shown by data published in the Journal of the National Cancer Institute.

Great progress has been made since the 1970s, but improvements in outcome have been less impressive for cancer patients aged 15-39 years, as shown by research published in Cancer.

Factors that contribute to the AYA gap

About 89,000 AYAs are diagnosed with cancer each year in the United States, according to data from the National Cancer Institute (NCI). Lymphomas and thyroid cancer are the most common cancers among younger AYAs, aged 15-24 years.

In a report commissioned by the NIH in 2006, many factors contributing to the AYA gap were identified. Chief among them were:

• Limitations in access to care.
• Delayed diagnosis.
• Inconsistency in treatment and follow-up.
• Long-term toxicity (fertility, second malignancies, and cardiovascular disease).

These factors compromise health-related survival, even when cancer-specific survival is improved.

Panelist Kara Kelly, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., noted that there are additional unique challenges for AYAs with cancer. These include:

• Pubertal changes.
• Developmental transition to independence.
• Societal impediments such as insurance coverage and disparities in access to specialized centers.
• Psychosocial factors such as health literacy and adherence to treatment and follow-up.

Focusing on lymphoma specifically, Dr. Kelly noted that lymphoma biology differs across the age spectrum and by race and ethnicity. Both tumor and host factors require further study, she said.
 

Clinical trial access for AYAs

Dr. Kelly emphasized that, unfortunately, clinical research participation is low among AYAs. A major impediment is that adult clinical trials historically required participants to be at least 18 years old.

In addition, there has not been a focused effort to educate AYAs about regulatory safeguards to ensure safety and the promise of enhanced benefit to them in NCI Cancer Trials Network (NCTN) trials. As a result, the refusal rate is high.

A multi-stakeholder workshop, convened in May 2016 by the American Society of Clinical Oncology and Friends of Cancer Research, outlined opportunities for expanding trial eligibility to include children younger than 18 years in first-in-human and other adult cancer clinical trials, enhancing their access to new agents, without compromising safety.

Recently, collaborative efforts between the adult and children’s NCTN research groups have included AYAs in studies addressing cancers that span the age spectrum, including lymphoma.

However, as Dr. Kelly noted, there are differences in AYA lymphoid malignancy types with a transition from more pediatric to more adult types.
 

Hodgkin lymphoma and primary mediastinal B-cell lymphoma

Panelist Lisa G. Roth, MD, of Weill Cornell Medicine, New York, reviewed the genomic landscape of Hodgkin lymphoma (HL) and primary mediastinal B-cell lymphoma (PMBCL).

Dr. Roth explained that both HL and PMBCL are derived from thymic B cells, predominantly affect the mediastinum, and are CD30-positive lymphomas. Both are characterized by upregulation of JAK/STAT and NF-kappaB as well as overexpression of PD-L1.

Dr. Roth noted that HL is challenging to sequence by standard methods because Reed Sternberg (HRS) cells represent less than 1% of the cellular infiltrate. Recurrently mutated genes in HL cluster by histologic subtype.

Whole-exome sequencing of HRS cells show loss of beta-2 microglobulin and MHC-1 expression, HLA-B, NF-kappaB signaling, and JAK-STAT signaling, according to data published in Blood Advances in 2019.

Dr. Roth’s lab performed immunohistochemistry on tissue microarrays in 145 cases of HL (unpublished data). Results showed that loss of beta-2 microglobulin is more common in younger HL patients. For other alterations, there were too few cases to know.

Dr. Roth’s lab is a member of a pediatric/AYA HL sequencing multi-institutional consortium that has been able to extract DNA and RNA from samples submitted for whole-exome sequencing. The consortium’s goal is to shed light on implications of other genomic alterations that may differ by age in HL patients.

Dr. Roth cited research showing that PMBCL shares molecular alterations similar to those of HL. Alterations in PMBCL suggest dysregulated cellular signaling and immune evasion mechanisms (e.g., deletions in MHC type 1 and 2, beta-2 microglobulin, JAK-STAT, and NF-kappaB mutations) that provide opportunities to study novel agents, according to data published in Blood in 2019.

By early 2021, the S1826 and ANHL1931 studies, which have no age restriction, will be available to AYA lymphoma patients with HL and PMBCL, respectively, Dr. Roth said.
 

Follicular lymphoma: Clinical features by age

Panelist Abner Louissaint Jr, MD, PhD, of Massachusetts General Hospital in Boston, discussed age-related differences in follicular lymphoma (FL).

He noted that FL typically presents at an advanced stage, with low- or high-grade histology. It is increasingly common in adults in their 50s and 60s, representing 20% of all lymphomas. FL is rare in children and AYAs.

Dr. Louissaint explained that the typical flow cytometric findings in FL are BCL2 translocations, occurring in up to 85%-90% of low-grade and 50% of high-grade cases. The t(14;18)(q32;q21) translocation juxtaposes BCL2 on 18q21 to regulatory sequences and enhances the expression of elements of the Ig heavy chain.

Malignant cells in FL patients express CD20, CD10, CD21, and BCL2 (in contrast to normal germinal centers) and overexpress BCL6 (in contrast to normal follicles), Dr. Louissaint noted. He said the Ki-67 proliferative index of the malignant cells is typically low.

Pediatric-type FL is rare, but case series show clinical, pathologic, and molecular features that are distinctive from adult FL, Dr. Louissaint explained.

He then discussed the features of pediatric-type FL in multiple domains. In the clinical domain, there is a male predilection, and stage tends to be low. There is frequent involvement of nodes of the head and neck region and rare involvement of internal lymph node chains.

Pathologically, the malignant cells appear high grade, with architectural effacement, expansile follicular pattern, large lymphocyte size, and an elevated proliferation index. In contrast to adult FL, malignant cells in pediatric-type FL lack aberrant BCL2 expression.

Most importantly, for pediatric-type FL, the prognosis is excellent with durable remissions after surgical excision, Dr. Louissaint said.
 

Follicular lymphoma: Molecular features by age

Because of the excellent prognosis in pediatric-type FL, it is important to assess whether young adults with FL have adult-type or pediatric-type lesions, Dr. Louissaint said.

He cited many studies showing differences in adult and pediatric-type FL. In adult FL, the mutational landscape is characterized by frequent chromatin-modifying mutations in genes such as CREBBP, KM22D, and EP300.

In contrast, in pediatric-type FL, there are frequent activating MAPK pathway mutations, including mutations in the negative regulatory domain of MAP2K1. These mutations are not seen in adult FL.

Dr. Louissaint noted that there may be mutations in epigenetic modifiers (CREBBP, TNFRSF14) in both adult and pediatric-type FL. However, CREBBP is very unusual in pediatric-type FL and common in adult FL. This suggests the alterations in pediatric-type FL do not simply represent an early stage of the same disease as adult FL.

Despite a high proliferating fraction and absence of BCL2/BCL6/IRF4 rearrangements in pediatric-type FL, the presence of these features was associated with dramatic difference in progression-free survival, according to research published in Blood in 2012.
 

A distinct entity

In 2016, the World Health Organization recognized pediatric-type FL as a distinct entity, with the following diagnostic criteria (published in Blood):

• At least partial effacement of nodal architecture, expansile follicles, intermediate-size blastoid cells, and no component of diffuse large B-cell lymphoma.
• Immunohistochemistry showing BCL6 positivity, BCL2 negativity or weak positivity, and a high proliferative fraction.
• Genomic studies showing no BCL2 amplification.
• Clinical features of nodal disease in the head and neck region, early clinical stage, age younger than 40 years, typically in a male with no internal nodes involved.

When FL occurs in AYAs, the diagnostic findings of pediatric-type FL suggest the patient will do well with conservative management (e.g., excision alone), Dr. Louissaint noted.
 

Two sizes do not fit all

The strategies that have improved cancer outcomes since the 1970s for children and older adults have been much less successful for AYAs with cancer.

As an oncologic community, we should not allow the AYA gap to persist. As always, the solutions are likely to involve focused clinical research, education, and communication. Effort will need to be targeted specifically to the AYA population.

Since health-related mortality is high even when cancer-specific outcomes improve, adopting and maintaining a healthy lifestyle must be a key part of the discussion with these young patients.

The biologic differences associated with AYA lymphomas demand participation in clinical trials.

Oncologists should vigorously support removing impediments to the participation of AYAs in prospective clinical trials, stratified (but unrestricted) by age, with careful analysis of patient-reported outcomes, late adverse effects, and biospecimen collection.

As Dr. Kelly noted in the question-and-answer period, the Children’s Oncology Group has an existing biobank of paraffin-embedded tumor samples, DNA from lymphoma specimens, plasma, and sera with clinically annotated data that can be given to investigators upon request and justification.
 

Going beyond eligibility for clinical trials

Unfortunately, we will likely find that broadening eligibility criteria is the “low-hanging fruit.” There are protocol-, patient-, and physician-related obstacles, according to a review published in Cancer in 2019.

Patient-related obstacles include fear of toxicity, uncertainty about placebos, a steep learning curve for health literacy, insurance-related impediments, and other access-related issues.

Discussions will need to be tailored to the AYA population. Frank, early conversations about fertility, sexuality, financial hardship, career advancement, work-life balance, and cognitive risks may not only facilitate treatment planning but also encourage the trust that is essential for patients to enroll in trials.

The investment in time, multidisciplinary staff and physician involvement, and potential delays in treatment initiation may be painful and inconvenient, but the benefits for long-term health outcomes and personal-professional relationships will be gratifying beyond measure.

Dr. Smith disclosed relationships with Genentech/Roche, Celgene, TGTX, Karyopharm, Janssen, and Bantem. Dr. Roth disclosed relationships with Janssen, ADC Therapeutics, and Celgene. Dr. Kelly and Dr. Louissaint had no financial relationships to disclose.



Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

The Food and Drug Administration recently approved tafasitamab-cxix (Monjuvi) in combination with lenalidomide for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, who are not eligible for autologous stem cell transplant (ASCT).

In an interview, Ann S. LaCasce, MD, a lymphoma specialist, associate professor of medicine at Harvard Medical School, and director of the Dana-Farber/Massachusetts General Brigham fellowship in hematology/oncology, discussed the drug and its approval:

Question: How common is relapsed or refractory DLBCL? Have there been any changes in the rates of this disease in recent years?

Dr. LaCasce: Approximately 40% of patients with DLBCL will have relapsed or refractory disease. The rates of lymphoma have been rising over the past several decades for unclear reasons. As this is a disease predominantly of older adults, increasing life expectancy likely plays a role. Environmental factors may also be contributing.

Q: How long do patients with relapsed or refractory DLBCL who are not eligible for stem cell transplant usually survive?

Dr. LaCasce: This is highly variable, though it’s estimated to be approximately 1 year. Some patients will be cured with autologous transplantation or CAR-T cells. The pace of the disease can be highly variable, with some patients responding to multiple lines of therapy whereas others may have rapidly progressive refractory disease.

Q: What makes patients with relapsed or refractory DLBCL ineligible for ASCT?

Dr. LaCasce: To be eligible, patients need to be younger than 70-75 years or so without significant comorbidities and must have chemotherapy-responsive disease. More than half of patients will not fit these criteria.

Q: Can you briefly describe the L-MIND study that led to the approval of tafasitamab-cxix?

Dr. LaCasce: This was a single-arm, phase 2 study of tafasitamab plus lenalidomide in patients with relapsed/refractory DLBCL status after one to three prior regimens who were not candidates for ASCT. Patients received tafasitamab until progression and up to 1 year of lenalidomide. The median age was 72 years, and 50% of patients had received only one prior line of therapy.

The overall and complete response rates in 80 patients treated were 60% and 43%, respectively. The median progression-free survival was approximately 1 year. Nearly half of patients required dose reduction of lenalidomide, and about a quarter discontinued the drug. Twenty-five percent of patients discontinued therapy for adverse events.

Q: What’s the toxicity profile of tafasitamab-cxix?

Dr. LaCasce: The most common adverse events were infusion reactions and myelosuppression, which are managed with standard approaches to incident rate ratios with steroids, antihistamines, etc. Myelosuppression can occur, but in this combination is mostly driven by lenalidomide, which is dose reduced or discontinued.

Q: Where does tafasitamab-cxix fit in the treatment paradigm for relapsed or refractory DLBCL? How does it compare with other available options?

Dr. LaCasce: This is an option for patients who are not candidates for potentially curative approaches, including ASCT and CAR T-cell therapy. There are patients not eligible for ASCT who may be appropriate for CAR-T.

Tafasitamab plus lenalidomide requires frequent visits, particularly during the first 3 months, and then every other week until progression. The dose of lenalidomide will not be tolerable for many of these patients.

Other options in this population include polatuzumab plus bendamustine/rituximab or possibly selinexor. The former has similar activity and is time limited, though many patients will not tolerate the full dose of bendamustine. In the study leading to approval, selinexor had a much lower response rate of approximately 30%, and the patient population was much more favorable, given that eligibility required 60-98 days after last therapy before enrolling.

The only approval specific for nontransplant patients is tafasitamab/lenalidomide.

Q: From a cost standpoint, how does tafasitamab compare with other options in this patient population?

Dr. LaCasce: I don’t have exact figures, but all options are very expensive. CAR-T is the most expensive. Given the ongoing therapy of tafasitamab until progression, the cumulative cost could be very high. Polatuzumab plus bendamustine/rituximab and selinexor are also very costly.

Q: What other drugs are in development for relapsed or refractory DLBCL?

Dr. LaCasce: Novel CAR T-cell therapies, including lisocabtagene maraleucel that is at the FDA, are in development. Bispecific antibodies (REGN1979 and mosunetuzumab), combinations with CD47 antibodies, and loncastuximab tesirine are all in phase 2 trials.

Dr. LaCasce has disclosed no relevant financial relationships.

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

The Food and Drug Administration recently approved tafasitamab-cxix (Monjuvi) in combination with lenalidomide for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, who are not eligible for autologous stem cell transplant (ASCT).

In an interview, Ann S. LaCasce, MD, a lymphoma specialist, associate professor of medicine at Harvard Medical School, and director of the Dana-Farber/Massachusetts General Brigham fellowship in hematology/oncology, discussed the drug and its approval:

Question: How common is relapsed or refractory DLBCL? Have there been any changes in the rates of this disease in recent years?

Dr. LaCasce: Approximately 40% of patients with DLBCL will have relapsed or refractory disease. The rates of lymphoma have been rising over the past several decades for unclear reasons. As this is a disease predominantly of older adults, increasing life expectancy likely plays a role. Environmental factors may also be contributing.

Q: How long do patients with relapsed or refractory DLBCL who are not eligible for stem cell transplant usually survive?

Dr. LaCasce: This is highly variable, though it’s estimated to be approximately 1 year. Some patients will be cured with autologous transplantation or CAR-T cells. The pace of the disease can be highly variable, with some patients responding to multiple lines of therapy whereas others may have rapidly progressive refractory disease.

Q: What makes patients with relapsed or refractory DLBCL ineligible for ASCT?

Dr. LaCasce: To be eligible, patients need to be younger than 70-75 years or so without significant comorbidities and must have chemotherapy-responsive disease. More than half of patients will not fit these criteria.

Q: Can you briefly describe the L-MIND study that led to the approval of tafasitamab-cxix?

Dr. LaCasce: This was a single-arm, phase 2 study of tafasitamab plus lenalidomide in patients with relapsed/refractory DLBCL status after one to three prior regimens who were not candidates for ASCT. Patients received tafasitamab until progression and up to 1 year of lenalidomide. The median age was 72 years, and 50% of patients had received only one prior line of therapy.

The overall and complete response rates in 80 patients treated were 60% and 43%, respectively. The median progression-free survival was approximately 1 year. Nearly half of patients required dose reduction of lenalidomide, and about a quarter discontinued the drug. Twenty-five percent of patients discontinued therapy for adverse events.

Q: What’s the toxicity profile of tafasitamab-cxix?

Dr. LaCasce: The most common adverse events were infusion reactions and myelosuppression, which are managed with standard approaches to incident rate ratios with steroids, antihistamines, etc. Myelosuppression can occur, but in this combination is mostly driven by lenalidomide, which is dose reduced or discontinued.

Q: Where does tafasitamab-cxix fit in the treatment paradigm for relapsed or refractory DLBCL? How does it compare with other available options?

Dr. LaCasce: This is an option for patients who are not candidates for potentially curative approaches, including ASCT and CAR T-cell therapy. There are patients not eligible for ASCT who may be appropriate for CAR-T.

Tafasitamab plus lenalidomide requires frequent visits, particularly during the first 3 months, and then every other week until progression. The dose of lenalidomide will not be tolerable for many of these patients.

Other options in this population include polatuzumab plus bendamustine/rituximab or possibly selinexor. The former has similar activity and is time limited, though many patients will not tolerate the full dose of bendamustine. In the study leading to approval, selinexor had a much lower response rate of approximately 30%, and the patient population was much more favorable, given that eligibility required 60-98 days after last therapy before enrolling.

The only approval specific for nontransplant patients is tafasitamab/lenalidomide.

Q: From a cost standpoint, how does tafasitamab compare with other options in this patient population?

Dr. LaCasce: I don’t have exact figures, but all options are very expensive. CAR-T is the most expensive. Given the ongoing therapy of tafasitamab until progression, the cumulative cost could be very high. Polatuzumab plus bendamustine/rituximab and selinexor are also very costly.

Q: What other drugs are in development for relapsed or refractory DLBCL?

Dr. LaCasce: Novel CAR T-cell therapies, including lisocabtagene maraleucel that is at the FDA, are in development. Bispecific antibodies (REGN1979 and mosunetuzumab), combinations with CD47 antibodies, and loncastuximab tesirine are all in phase 2 trials.

Dr. LaCasce has disclosed no relevant financial relationships.

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

The Food and Drug Administration recently approved tafasitamab-cxix (Monjuvi) in combination with lenalidomide for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, who are not eligible for autologous stem cell transplant (ASCT).

In an interview, Ann S. LaCasce, MD, a lymphoma specialist, associate professor of medicine at Harvard Medical School, and director of the Dana-Farber/Massachusetts General Brigham fellowship in hematology/oncology, discussed the drug and its approval:

Question: How common is relapsed or refractory DLBCL? Have there been any changes in the rates of this disease in recent years?

Dr. LaCasce: Approximately 40% of patients with DLBCL will have relapsed or refractory disease. The rates of lymphoma have been rising over the past several decades for unclear reasons. As this is a disease predominantly of older adults, increasing life expectancy likely plays a role. Environmental factors may also be contributing.

Q: How long do patients with relapsed or refractory DLBCL who are not eligible for stem cell transplant usually survive?

Dr. LaCasce: This is highly variable, though it’s estimated to be approximately 1 year. Some patients will be cured with autologous transplantation or CAR-T cells. The pace of the disease can be highly variable, with some patients responding to multiple lines of therapy whereas others may have rapidly progressive refractory disease.

Q: What makes patients with relapsed or refractory DLBCL ineligible for ASCT?

Dr. LaCasce: To be eligible, patients need to be younger than 70-75 years or so without significant comorbidities and must have chemotherapy-responsive disease. More than half of patients will not fit these criteria.

Q: Can you briefly describe the L-MIND study that led to the approval of tafasitamab-cxix?

Dr. LaCasce: This was a single-arm, phase 2 study of tafasitamab plus lenalidomide in patients with relapsed/refractory DLBCL status after one to three prior regimens who were not candidates for ASCT. Patients received tafasitamab until progression and up to 1 year of lenalidomide. The median age was 72 years, and 50% of patients had received only one prior line of therapy.

The overall and complete response rates in 80 patients treated were 60% and 43%, respectively. The median progression-free survival was approximately 1 year. Nearly half of patients required dose reduction of lenalidomide, and about a quarter discontinued the drug. Twenty-five percent of patients discontinued therapy for adverse events.

Q: What’s the toxicity profile of tafasitamab-cxix?

Dr. LaCasce: The most common adverse events were infusion reactions and myelosuppression, which are managed with standard approaches to incident rate ratios with steroids, antihistamines, etc. Myelosuppression can occur, but in this combination is mostly driven by lenalidomide, which is dose reduced or discontinued.

Q: Where does tafasitamab-cxix fit in the treatment paradigm for relapsed or refractory DLBCL? How does it compare with other available options?

Dr. LaCasce: This is an option for patients who are not candidates for potentially curative approaches, including ASCT and CAR T-cell therapy. There are patients not eligible for ASCT who may be appropriate for CAR-T.

Tafasitamab plus lenalidomide requires frequent visits, particularly during the first 3 months, and then every other week until progression. The dose of lenalidomide will not be tolerable for many of these patients.

Other options in this population include polatuzumab plus bendamustine/rituximab or possibly selinexor. The former has similar activity and is time limited, though many patients will not tolerate the full dose of bendamustine. In the study leading to approval, selinexor had a much lower response rate of approximately 30%, and the patient population was much more favorable, given that eligibility required 60-98 days after last therapy before enrolling.

The only approval specific for nontransplant patients is tafasitamab/lenalidomide.

Q: From a cost standpoint, how does tafasitamab compare with other options in this patient population?

Dr. LaCasce: I don’t have exact figures, but all options are very expensive. CAR-T is the most expensive. Given the ongoing therapy of tafasitamab until progression, the cumulative cost could be very high. Polatuzumab plus bendamustine/rituximab and selinexor are also very costly.

Q: What other drugs are in development for relapsed or refractory DLBCL?

Dr. LaCasce: Novel CAR T-cell therapies, including lisocabtagene maraleucel that is at the FDA, are in development. Bispecific antibodies (REGN1979 and mosunetuzumab), combinations with CD47 antibodies, and loncastuximab tesirine are all in phase 2 trials.

Dr. LaCasce has disclosed no relevant financial relationships.

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

Mortality in patients with COVID-19 and cancer is associated with general clinical and demographic factors, cancer-specific factors, cancer treatment variables, and laboratory parameters, according to two presentations at the European Society for Medical Oncology Virtual Congress 2020.

Two analyses of data from the COVID-19 and Cancer Consortium (CCC19) were presented at the meeting.

The data suggest that older age, male sex, more comorbidities, poor performance status, progressive cancer or multiple cancers, hematologic malignancy, and recent cancer therapy are all associated with higher mortality among patients with cancer and COVID-19. Anti-CD20 therapy is associated with an especially high mortality rate, according to an investigator.

Among hospitalized patients, increased absolute neutrophil count as well as abnormal D-dimer, high-sensitivity troponin, and C-reactive protein are associated with a higher risk of mortality.

Prior analyses of CCC19 data pointed to several factors associated with higher COVID-19 death rates, according to Petros Grivas, MD, PhD, of University of Washington, Seattle, who presented some CCC19 data at the meeting. However, the prior analyses were limited by weak statistical power and low event rates, Dr. Grivas said.
 

Clinical and laboratory factors: Abstract LBA72

The aim of Dr. Grivas’s analysis was to validate a priori identified demographic and clinicopathologic factors associated with 30-day all-cause mortality in patients with COVID-19 and cancer. Dr. Grivas and colleagues also explored the potential association between laboratory parameters and 30-day all-cause mortality.

The analysis included 3,899 patients with cancer and COVID-19 from 124 centers. Most centers are in the United States, but 4% are in Canada, and 2% are in Spain. About two-thirds of patients were 60 years of age or younger at baseline, half were men, 79% had solid tumors, and 21% had hematologic malignancies.

Cancer-specific factors associated with an increased risk of 30-day all-cause mortality were having progressive cancer (adjusted odds ratio, 2.9), receiving cancer therapy within 3 months (aOR, 1.2), having a hematologic versus solid tumor (aOR, 1.7), and having multiple malignancies (aOR, 1.5).

Clinical factors associated with an increased risk of 30-day all-cause mortality were Black versus White race (aOR, 1.5), older age (aOR, 1.7 per 10 years), three or more actively treated comorbidities (versus none; aOR, 2.1), and Eastern Cooperative Oncology Group performance status of 2 or more (versus 0; aOR, 4.6).

In hospitalized patients, several laboratory variables were associated with an increased risk of 30-day all-cause mortality. Having an absolute neutrophil count above the upper limit of normal doubled the risk (aOR, 2.0), while abnormal D-dimer, high-sensitivity troponin, and C-reactive protein all more than doubled the risk of mortality (aORs of 2.5, 2.5, and 2.4, respectively).

Further risk modeling with multivariable analysis will be performed after longer follow-up, Dr. Grivas noted.
 

Treatment-related outcomes: Abstract LBA71

An additional analysis of CCC19 data encompassed 3,654 patients. In this analysis, researchers investigated the correlation between timing of cancer treatment and COVID-19–related complications and 30-day mortality.

Mortality was highest among cancer patients treated 1-3 months prior to COVID-19 diagnosis, with all-cause mortality at 28%, said Trisha M. Wise-Draper, MD, PhD, of University of Cincinnati, when presenting the data at the meeting.

Rates for other complications (hospitalization, oxygen required, ICU admission, and mechanical ventilation) were similar regardless of treatment timing.

The unadjusted 30-day mortality rate was highest for patients treated most recently with chemoimmunotherapy (30%), followed by chemotherapy (18%), chemoradiotherapy (18%), and targeted therapy (17%).

The mortality rate was “particularly high,” at 50%, in patients receiving anti-CD20 therapy 1-3 months prior to COVID-19 diagnosis – the time period for which significant B-cell depletion develops, Dr. Wise-Draper observed.

An analysis of disease status among 1,449 patients treated within 3 months of COVID-19 diagnosis showed mortality risk increasing from 6% among patients in remission or with newly emergent disease, to 22% in patients with any active cancer, to 34% in those with progressing disease, Dr. Wise-Draper said.

Discussant Benjamin Solomon, MD, PhD, of Peter MacCallum Cancer Centre in Melbourne, made note of the high 30-day mortality rate seen in patients receiving anti-CD20 therapy as well as the elevated standardized mortality ratios with recent chemoimmunotherapy and targeted therapy.

“Although there are some limitations of this analysis, it provides the best data we have to date about the effects of treatment on early mortality in patients with COVID-19 and cancer. It points to a modest but heterogeneous effect of treatment on outcome, one which is likely to become clearer with larger cohorts and additional analysis,” Dr. Solomon said.

This research was funded by the American Cancer Society, Hope Foundation for Cancer Research, Jim and Carol O’Hare Fund, National Cancer Institute, National Human Genome Research Institute, Vanderbilt Institute for Clinical and Translational Research, and Fonds de Recherche du Quebec-Sante. Dr. Grivas disclosed relationships with many companies, but none are related to this work. Dr. Wise-Draper disclosed relationships with Merck, Bristol-Myers Squibb, Tesaro, GlaxoSmithKline, AstraZeneca, Shattuck Labs, and Rakuten. Dr. Solomon disclosed relationships with Amgen, AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Pfizer, and Roche-Genentech.

SOURCES: Grivas P et al. ESMO 2020, Abstract LBA72; Wise-Draper TM et al. ESMO 2020, Abstract LBA71.

Mortality in patients with COVID-19 and cancer is associated with general clinical and demographic factors, cancer-specific factors, cancer treatment variables, and laboratory parameters, according to two presentations at the European Society for Medical Oncology Virtual Congress 2020.

Two analyses of data from the COVID-19 and Cancer Consortium (CCC19) were presented at the meeting.

The data suggest that older age, male sex, more comorbidities, poor performance status, progressive cancer or multiple cancers, hematologic malignancy, and recent cancer therapy are all associated with higher mortality among patients with cancer and COVID-19. Anti-CD20 therapy is associated with an especially high mortality rate, according to an investigator.

Among hospitalized patients, increased absolute neutrophil count as well as abnormal D-dimer, high-sensitivity troponin, and C-reactive protein are associated with a higher risk of mortality.

Prior analyses of CCC19 data pointed to several factors associated with higher COVID-19 death rates, according to Petros Grivas, MD, PhD, of University of Washington, Seattle, who presented some CCC19 data at the meeting. However, the prior analyses were limited by weak statistical power and low event rates, Dr. Grivas said.
 

Clinical and laboratory factors: Abstract LBA72

The aim of Dr. Grivas’s analysis was to validate a priori identified demographic and clinicopathologic factors associated with 30-day all-cause mortality in patients with COVID-19 and cancer. Dr. Grivas and colleagues also explored the potential association between laboratory parameters and 30-day all-cause mortality.

The analysis included 3,899 patients with cancer and COVID-19 from 124 centers. Most centers are in the United States, but 4% are in Canada, and 2% are in Spain. About two-thirds of patients were 60 years of age or younger at baseline, half were men, 79% had solid tumors, and 21% had hematologic malignancies.

Cancer-specific factors associated with an increased risk of 30-day all-cause mortality were having progressive cancer (adjusted odds ratio, 2.9), receiving cancer therapy within 3 months (aOR, 1.2), having a hematologic versus solid tumor (aOR, 1.7), and having multiple malignancies (aOR, 1.5).

Clinical factors associated with an increased risk of 30-day all-cause mortality were Black versus White race (aOR, 1.5), older age (aOR, 1.7 per 10 years), three or more actively treated comorbidities (versus none; aOR, 2.1), and Eastern Cooperative Oncology Group performance status of 2 or more (versus 0; aOR, 4.6).

In hospitalized patients, several laboratory variables were associated with an increased risk of 30-day all-cause mortality. Having an absolute neutrophil count above the upper limit of normal doubled the risk (aOR, 2.0), while abnormal D-dimer, high-sensitivity troponin, and C-reactive protein all more than doubled the risk of mortality (aORs of 2.5, 2.5, and 2.4, respectively).

Further risk modeling with multivariable analysis will be performed after longer follow-up, Dr. Grivas noted.
 

Treatment-related outcomes: Abstract LBA71

An additional analysis of CCC19 data encompassed 3,654 patients. In this analysis, researchers investigated the correlation between timing of cancer treatment and COVID-19–related complications and 30-day mortality.

Mortality was highest among cancer patients treated 1-3 months prior to COVID-19 diagnosis, with all-cause mortality at 28%, said Trisha M. Wise-Draper, MD, PhD, of University of Cincinnati, when presenting the data at the meeting.

Rates for other complications (hospitalization, oxygen required, ICU admission, and mechanical ventilation) were similar regardless of treatment timing.

The unadjusted 30-day mortality rate was highest for patients treated most recently with chemoimmunotherapy (30%), followed by chemotherapy (18%), chemoradiotherapy (18%), and targeted therapy (17%).

The mortality rate was “particularly high,” at 50%, in patients receiving anti-CD20 therapy 1-3 months prior to COVID-19 diagnosis – the time period for which significant B-cell depletion develops, Dr. Wise-Draper observed.

An analysis of disease status among 1,449 patients treated within 3 months of COVID-19 diagnosis showed mortality risk increasing from 6% among patients in remission or with newly emergent disease, to 22% in patients with any active cancer, to 34% in those with progressing disease, Dr. Wise-Draper said.

Discussant Benjamin Solomon, MD, PhD, of Peter MacCallum Cancer Centre in Melbourne, made note of the high 30-day mortality rate seen in patients receiving anti-CD20 therapy as well as the elevated standardized mortality ratios with recent chemoimmunotherapy and targeted therapy.

“Although there are some limitations of this analysis, it provides the best data we have to date about the effects of treatment on early mortality in patients with COVID-19 and cancer. It points to a modest but heterogeneous effect of treatment on outcome, one which is likely to become clearer with larger cohorts and additional analysis,” Dr. Solomon said.

This research was funded by the American Cancer Society, Hope Foundation for Cancer Research, Jim and Carol O’Hare Fund, National Cancer Institute, National Human Genome Research Institute, Vanderbilt Institute for Clinical and Translational Research, and Fonds de Recherche du Quebec-Sante. Dr. Grivas disclosed relationships with many companies, but none are related to this work. Dr. Wise-Draper disclosed relationships with Merck, Bristol-Myers Squibb, Tesaro, GlaxoSmithKline, AstraZeneca, Shattuck Labs, and Rakuten. Dr. Solomon disclosed relationships with Amgen, AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Pfizer, and Roche-Genentech.

SOURCES: Grivas P et al. ESMO 2020, Abstract LBA72; Wise-Draper TM et al. ESMO 2020, Abstract LBA71.

Mortality in patients with COVID-19 and cancer is associated with general clinical and demographic factors, cancer-specific factors, cancer treatment variables, and laboratory parameters, according to two presentations at the European Society for Medical Oncology Virtual Congress 2020.

Two analyses of data from the COVID-19 and Cancer Consortium (CCC19) were presented at the meeting.

The data suggest that older age, male sex, more comorbidities, poor performance status, progressive cancer or multiple cancers, hematologic malignancy, and recent cancer therapy are all associated with higher mortality among patients with cancer and COVID-19. Anti-CD20 therapy is associated with an especially high mortality rate, according to an investigator.

Among hospitalized patients, increased absolute neutrophil count as well as abnormal D-dimer, high-sensitivity troponin, and C-reactive protein are associated with a higher risk of mortality.

Prior analyses of CCC19 data pointed to several factors associated with higher COVID-19 death rates, according to Petros Grivas, MD, PhD, of University of Washington, Seattle, who presented some CCC19 data at the meeting. However, the prior analyses were limited by weak statistical power and low event rates, Dr. Grivas said.
 

Clinical and laboratory factors: Abstract LBA72

The aim of Dr. Grivas’s analysis was to validate a priori identified demographic and clinicopathologic factors associated with 30-day all-cause mortality in patients with COVID-19 and cancer. Dr. Grivas and colleagues also explored the potential association between laboratory parameters and 30-day all-cause mortality.

The analysis included 3,899 patients with cancer and COVID-19 from 124 centers. Most centers are in the United States, but 4% are in Canada, and 2% are in Spain. About two-thirds of patients were 60 years of age or younger at baseline, half were men, 79% had solid tumors, and 21% had hematologic malignancies.

Cancer-specific factors associated with an increased risk of 30-day all-cause mortality were having progressive cancer (adjusted odds ratio, 2.9), receiving cancer therapy within 3 months (aOR, 1.2), having a hematologic versus solid tumor (aOR, 1.7), and having multiple malignancies (aOR, 1.5).

Clinical factors associated with an increased risk of 30-day all-cause mortality were Black versus White race (aOR, 1.5), older age (aOR, 1.7 per 10 years), three or more actively treated comorbidities (versus none; aOR, 2.1), and Eastern Cooperative Oncology Group performance status of 2 or more (versus 0; aOR, 4.6).

In hospitalized patients, several laboratory variables were associated with an increased risk of 30-day all-cause mortality. Having an absolute neutrophil count above the upper limit of normal doubled the risk (aOR, 2.0), while abnormal D-dimer, high-sensitivity troponin, and C-reactive protein all more than doubled the risk of mortality (aORs of 2.5, 2.5, and 2.4, respectively).

Further risk modeling with multivariable analysis will be performed after longer follow-up, Dr. Grivas noted.
 

Treatment-related outcomes: Abstract LBA71

An additional analysis of CCC19 data encompassed 3,654 patients. In this analysis, researchers investigated the correlation between timing of cancer treatment and COVID-19–related complications and 30-day mortality.

Mortality was highest among cancer patients treated 1-3 months prior to COVID-19 diagnosis, with all-cause mortality at 28%, said Trisha M. Wise-Draper, MD, PhD, of University of Cincinnati, when presenting the data at the meeting.

Rates for other complications (hospitalization, oxygen required, ICU admission, and mechanical ventilation) were similar regardless of treatment timing.

The unadjusted 30-day mortality rate was highest for patients treated most recently with chemoimmunotherapy (30%), followed by chemotherapy (18%), chemoradiotherapy (18%), and targeted therapy (17%).

The mortality rate was “particularly high,” at 50%, in patients receiving anti-CD20 therapy 1-3 months prior to COVID-19 diagnosis – the time period for which significant B-cell depletion develops, Dr. Wise-Draper observed.

An analysis of disease status among 1,449 patients treated within 3 months of COVID-19 diagnosis showed mortality risk increasing from 6% among patients in remission or with newly emergent disease, to 22% in patients with any active cancer, to 34% in those with progressing disease, Dr. Wise-Draper said.

Discussant Benjamin Solomon, MD, PhD, of Peter MacCallum Cancer Centre in Melbourne, made note of the high 30-day mortality rate seen in patients receiving anti-CD20 therapy as well as the elevated standardized mortality ratios with recent chemoimmunotherapy and targeted therapy.

“Although there are some limitations of this analysis, it provides the best data we have to date about the effects of treatment on early mortality in patients with COVID-19 and cancer. It points to a modest but heterogeneous effect of treatment on outcome, one which is likely to become clearer with larger cohorts and additional analysis,” Dr. Solomon said.

This research was funded by the American Cancer Society, Hope Foundation for Cancer Research, Jim and Carol O’Hare Fund, National Cancer Institute, National Human Genome Research Institute, Vanderbilt Institute for Clinical and Translational Research, and Fonds de Recherche du Quebec-Sante. Dr. Grivas disclosed relationships with many companies, but none are related to this work. Dr. Wise-Draper disclosed relationships with Merck, Bristol-Myers Squibb, Tesaro, GlaxoSmithKline, AstraZeneca, Shattuck Labs, and Rakuten. Dr. Solomon disclosed relationships with Amgen, AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Pfizer, and Roche-Genentech.

SOURCES: Grivas P et al. ESMO 2020, Abstract LBA72; Wise-Draper TM et al. ESMO 2020, Abstract LBA71.

A substantial cumulative burden of treatment in the first year is borne by patients newly diagnosed with multiple myeloma (MM), according to a report published online in Clinical Lymphoma, Myeloma and Leukemia.

MM is a disease of aging, with a median age at diagnosis of 69 years, and the burden of treatment and not just possible outcomes should be considered in decision-making discussions with patients, according to researchers Hira S. Mian, MD, of McMaster University, Hamilton, Ont., and colleagues.

They performed a retrospective study of a Medicare-linked database of 3,065 adults newly diagnosed with multiple myeloma (MM) between 2007-2013. The treatment burden among the patients was assessed to determine those factors associated with high treatment burden.
 

Heavy burden

Treatment burden was defined as the number of total days with a health care encounter (including acute care and outpatient visits), oncology and nononcology physician visits, and the number of new prescriptions within the first year following diagnosis, according to the researchers.

The study found that there was a substantial burden of treatment, including a median of more than 2 months of cumulative interactions with health care, within the first year following diagnosis. This burden was highest during the first 3 months.

Those patients who had multiple comorbidities (adjusted odds ratio [aOR] 1.27 per 1-point increase in Charlson comorbidity index, P < .001), poor performance status (aOR 1.85, P < .001), myeloma-related end-organ damage, especially bone disease (aOR 2.28, P < .001), and those who received autologous stem cell transplant (aOR 2.41, P < .001) were more likely to have a higher treatment burden, they reported.

“Decision-making regarding treatment modalities should not just emphasize traditional parameters such as response rates and progression-free survival but should also include a discussion regarding the workload burden placed on the patient and the care partner, in order to ensure informed and patient-centered decision-making is prioritized. This may be particularly relevant among certain subgroups such as older patients with cancer who may prioritize quality of life over aggressive disease control and overall survival,” the researchers concluded.

The study was funded by the National Cancer Institute at the U.S. National Institutes of Health. The authors reported funding from a variety of pharmaceutical and biotechnology companies.

[email protected]

SOURCE: Mian HS et al. Clin Lymphoma Myeloma Leuk. 2020 Oct 1. doi: 10.1016/j.clml.2020.09.010.

A substantial cumulative burden of treatment in the first year is borne by patients newly diagnosed with multiple myeloma (MM), according to a report published online in Clinical Lymphoma, Myeloma and Leukemia.

MM is a disease of aging, with a median age at diagnosis of 69 years, and the burden of treatment and not just possible outcomes should be considered in decision-making discussions with patients, according to researchers Hira S. Mian, MD, of McMaster University, Hamilton, Ont., and colleagues.

They performed a retrospective study of a Medicare-linked database of 3,065 adults newly diagnosed with multiple myeloma (MM) between 2007-2013. The treatment burden among the patients was assessed to determine those factors associated with high treatment burden.
 

Heavy burden

Treatment burden was defined as the number of total days with a health care encounter (including acute care and outpatient visits), oncology and nononcology physician visits, and the number of new prescriptions within the first year following diagnosis, according to the researchers.

The study found that there was a substantial burden of treatment, including a median of more than 2 months of cumulative interactions with health care, within the first year following diagnosis. This burden was highest during the first 3 months.

Those patients who had multiple comorbidities (adjusted odds ratio [aOR] 1.27 per 1-point increase in Charlson comorbidity index, P < .001), poor performance status (aOR 1.85, P < .001), myeloma-related end-organ damage, especially bone disease (aOR 2.28, P < .001), and those who received autologous stem cell transplant (aOR 2.41, P < .001) were more likely to have a higher treatment burden, they reported.

“Decision-making regarding treatment modalities should not just emphasize traditional parameters such as response rates and progression-free survival but should also include a discussion regarding the workload burden placed on the patient and the care partner, in order to ensure informed and patient-centered decision-making is prioritized. This may be particularly relevant among certain subgroups such as older patients with cancer who may prioritize quality of life over aggressive disease control and overall survival,” the researchers concluded.

The study was funded by the National Cancer Institute at the U.S. National Institutes of Health. The authors reported funding from a variety of pharmaceutical and biotechnology companies.

[email protected]

SOURCE: Mian HS et al. Clin Lymphoma Myeloma Leuk. 2020 Oct 1. doi: 10.1016/j.clml.2020.09.010.

A substantial cumulative burden of treatment in the first year is borne by patients newly diagnosed with multiple myeloma (MM), according to a report published online in Clinical Lymphoma, Myeloma and Leukemia.

MM is a disease of aging, with a median age at diagnosis of 69 years, and the burden of treatment and not just possible outcomes should be considered in decision-making discussions with patients, according to researchers Hira S. Mian, MD, of McMaster University, Hamilton, Ont., and colleagues.

They performed a retrospective study of a Medicare-linked database of 3,065 adults newly diagnosed with multiple myeloma (MM) between 2007-2013. The treatment burden among the patients was assessed to determine those factors associated with high treatment burden.
 

Heavy burden

Treatment burden was defined as the number of total days with a health care encounter (including acute care and outpatient visits), oncology and nononcology physician visits, and the number of new prescriptions within the first year following diagnosis, according to the researchers.

The study found that there was a substantial burden of treatment, including a median of more than 2 months of cumulative interactions with health care, within the first year following diagnosis. This burden was highest during the first 3 months.

Those patients who had multiple comorbidities (adjusted odds ratio [aOR] 1.27 per 1-point increase in Charlson comorbidity index, P < .001), poor performance status (aOR 1.85, P < .001), myeloma-related end-organ damage, especially bone disease (aOR 2.28, P < .001), and those who received autologous stem cell transplant (aOR 2.41, P < .001) were more likely to have a higher treatment burden, they reported.

“Decision-making regarding treatment modalities should not just emphasize traditional parameters such as response rates and progression-free survival but should also include a discussion regarding the workload burden placed on the patient and the care partner, in order to ensure informed and patient-centered decision-making is prioritized. This may be particularly relevant among certain subgroups such as older patients with cancer who may prioritize quality of life over aggressive disease control and overall survival,” the researchers concluded.

The study was funded by the National Cancer Institute at the U.S. National Institutes of Health. The authors reported funding from a variety of pharmaceutical and biotechnology companies.

[email protected]

SOURCE: Mian HS et al. Clin Lymphoma Myeloma Leuk. 2020 Oct 1. doi: 10.1016/j.clml.2020.09.010.

Acalabrutinib, given alone or in combination with obinutuzumab, showed favorable progression-free survival (PFS) and overall survival (OS), compared with other frontline therapies for chronic lymphocytic leukemia (CLL) in fludarabine-ineligible patients, according to the results of a meta-analysis comparing clinical trial results.

Researchers conducted a systematic literature review for applicable CLL studies that examined frontline treatments in order to compare the results with data on acalabrutinib (monotherapy and in combination with obinutuzumab) from patients in the ELEVATE-TN study (NCT02475681), according to a report published in Clinical Therapeutics.

Matthew S. Davids, MD, MMSc, of the Dana-Farber Cancer Institute in Boston, and colleagues performed a network meta-analysis (NMA) comparing acalabrutinib versus other standard frontline therapies for CLL in patients for whom fludarabine-based treatment is not appropriate.

“In the absence of head-to-head trial data, NMAs allow for simultaneous comparisons of a number of interventions with multiple comparators, by synthesizing direct and indirect evidence,” the authors stated.

Eight randomized controlled trials (RCTs) met the criteria for comparison.

The researchers constructed two evidence networks: Network A comprised solely RCTs that met the inclusion criteria, and Network B comprised seven RCTs and a published cross-trial comparison of ibrutinib from RESONATE-2 and chlorambucil plus obinutuzumab from iLLUMINATE. PFS and OS results were reported by using hazard ratios and 95% credible intervals.


 

Overall benefit

Both networks showed a significant improvement in PFS for acalabrutinib plus obinutuzumab over all comparators, according to the researchers. Both networks also showed a significant improvement in PFS for acalabrutinib monotherapy versus most comparators, with a significant difference to ibrutinib monotherapy found in Network A but not Network B.

Conversely, a significant difference in PFS was observed for acalabrutinib monotherapy versus venetoclax plus obinutuzumab in Network B but not Network A.

Overall survival hazard ratios ranged from 0.18 to 0.65 in favor of acalabrutinib-based treatment, but not all were significant. Acalabrutinib plus obinutuzumab ranked highest in terms of PFS and OS improvement, followed by acalabrutinib monotherapy.

“Although our NMAs provide useful insights into the relative efficacy of acalabrutinib, compared with other frontline treatments of CLL, the results cannot be considered confirmatory, and head-to-head randomized trials are needed, especially to compare the efficacy of acalabrutinib versus other targeted agents,” the researchers concluded.

AstraZeneca sponsored the study. The authors reported funding from AstraZeneca and numerous other pharmaceutical companies.

[email protected]

SOURCE: Davids MS et al. Clin Ther. 2020 Oct 5. doi: 10.1016/j.clinthera.2020.08.017.

Acalabrutinib, given alone or in combination with obinutuzumab, showed favorable progression-free survival (PFS) and overall survival (OS), compared with other frontline therapies for chronic lymphocytic leukemia (CLL) in fludarabine-ineligible patients, according to the results of a meta-analysis comparing clinical trial results.

Researchers conducted a systematic literature review for applicable CLL studies that examined frontline treatments in order to compare the results with data on acalabrutinib (monotherapy and in combination with obinutuzumab) from patients in the ELEVATE-TN study (NCT02475681), according to a report published in Clinical Therapeutics.

Matthew S. Davids, MD, MMSc, of the Dana-Farber Cancer Institute in Boston, and colleagues performed a network meta-analysis (NMA) comparing acalabrutinib versus other standard frontline therapies for CLL in patients for whom fludarabine-based treatment is not appropriate.

“In the absence of head-to-head trial data, NMAs allow for simultaneous comparisons of a number of interventions with multiple comparators, by synthesizing direct and indirect evidence,” the authors stated.

Eight randomized controlled trials (RCTs) met the criteria for comparison.

The researchers constructed two evidence networks: Network A comprised solely RCTs that met the inclusion criteria, and Network B comprised seven RCTs and a published cross-trial comparison of ibrutinib from RESONATE-2 and chlorambucil plus obinutuzumab from iLLUMINATE. PFS and OS results were reported by using hazard ratios and 95% credible intervals.


 

Overall benefit

Both networks showed a significant improvement in PFS for acalabrutinib plus obinutuzumab over all comparators, according to the researchers. Both networks also showed a significant improvement in PFS for acalabrutinib monotherapy versus most comparators, with a significant difference to ibrutinib monotherapy found in Network A but not Network B.

Conversely, a significant difference in PFS was observed for acalabrutinib monotherapy versus venetoclax plus obinutuzumab in Network B but not Network A.

Overall survival hazard ratios ranged from 0.18 to 0.65 in favor of acalabrutinib-based treatment, but not all were significant. Acalabrutinib plus obinutuzumab ranked highest in terms of PFS and OS improvement, followed by acalabrutinib monotherapy.

“Although our NMAs provide useful insights into the relative efficacy of acalabrutinib, compared with other frontline treatments of CLL, the results cannot be considered confirmatory, and head-to-head randomized trials are needed, especially to compare the efficacy of acalabrutinib versus other targeted agents,” the researchers concluded.

AstraZeneca sponsored the study. The authors reported funding from AstraZeneca and numerous other pharmaceutical companies.

[email protected]

SOURCE: Davids MS et al. Clin Ther. 2020 Oct 5. doi: 10.1016/j.clinthera.2020.08.017.

Acalabrutinib, given alone or in combination with obinutuzumab, showed favorable progression-free survival (PFS) and overall survival (OS), compared with other frontline therapies for chronic lymphocytic leukemia (CLL) in fludarabine-ineligible patients, according to the results of a meta-analysis comparing clinical trial results.

Researchers conducted a systematic literature review for applicable CLL studies that examined frontline treatments in order to compare the results with data on acalabrutinib (monotherapy and in combination with obinutuzumab) from patients in the ELEVATE-TN study (NCT02475681), according to a report published in Clinical Therapeutics.

Matthew S. Davids, MD, MMSc, of the Dana-Farber Cancer Institute in Boston, and colleagues performed a network meta-analysis (NMA) comparing acalabrutinib versus other standard frontline therapies for CLL in patients for whom fludarabine-based treatment is not appropriate.

“In the absence of head-to-head trial data, NMAs allow for simultaneous comparisons of a number of interventions with multiple comparators, by synthesizing direct and indirect evidence,” the authors stated.

Eight randomized controlled trials (RCTs) met the criteria for comparison.

The researchers constructed two evidence networks: Network A comprised solely RCTs that met the inclusion criteria, and Network B comprised seven RCTs and a published cross-trial comparison of ibrutinib from RESONATE-2 and chlorambucil plus obinutuzumab from iLLUMINATE. PFS and OS results were reported by using hazard ratios and 95% credible intervals.


 

Overall benefit

Both networks showed a significant improvement in PFS for acalabrutinib plus obinutuzumab over all comparators, according to the researchers. Both networks also showed a significant improvement in PFS for acalabrutinib monotherapy versus most comparators, with a significant difference to ibrutinib monotherapy found in Network A but not Network B.

Conversely, a significant difference in PFS was observed for acalabrutinib monotherapy versus venetoclax plus obinutuzumab in Network B but not Network A.

Overall survival hazard ratios ranged from 0.18 to 0.65 in favor of acalabrutinib-based treatment, but not all were significant. Acalabrutinib plus obinutuzumab ranked highest in terms of PFS and OS improvement, followed by acalabrutinib monotherapy.

“Although our NMAs provide useful insights into the relative efficacy of acalabrutinib, compared with other frontline treatments of CLL, the results cannot be considered confirmatory, and head-to-head randomized trials are needed, especially to compare the efficacy of acalabrutinib versus other targeted agents,” the researchers concluded.

AstraZeneca sponsored the study. The authors reported funding from AstraZeneca and numerous other pharmaceutical companies.

[email protected]

SOURCE: Davids MS et al. Clin Ther. 2020 Oct 5. doi: 10.1016/j.clinthera.2020.08.017.

Because of physiological changes with aging and differences in cancer biology, caring for older adults (OAs) with cancer requires careful assessment and planning.

Clark Dumontier, MD, of Brigham and Women’s Hospital in Boston, and colleagues sought to define the meaning of the terms “undertreatment” and “overtreatment” for OAs with cancer in a scoping literature review published in the Journal of Clinical Oncology.

Though OAs are typically defined as adults aged 65 years and older, in this review, the authors defined OAs as patients aged 60 years and older.

The authors theorized that a scoping review of papers about this patient population could provide clues about limitations in the oncology literature and guidance about patient management and future research. Despite comprising the majority of cancer patients, OAs are underrepresented in clinical trials.
 

About scoping reviews

Scoping reviews are used to identify existing evidence in a field, clarify concepts or definitions in the literature, survey how research on a topic is conducted, and identify knowledge gaps. In addition, scoping reviews summarize available evidence without answering a discrete research question.

Industry standards for scoping reviews have been established by the Johanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. According to these standards, scoping reviews should:

• Establish eligibility criteria with a rationale for each criterion clearly explained
• Search multiple databases in multiple languages
• Include “gray literature,” defined as studies that are unpublished or difficult to locate
• Have several independent reviewers screen titles and abstracts
• Ask multiple independent reviewers to review full text articles
• Present results with charts or diagrams that align with the review’s objective
• Graphically depict the decision process for including/excluding sources
• Identify implications for further research.

In their review, Dr. DuMontier and colleagues fulfilled many of the aforementioned criteria. The team searched three English-language databases for titles and abstracts that included the terms undertreatment and/or overtreatment, and were related to OAs with cancer, inclusive of all types of articles, cancer types, and treatments.

Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived. Within a random subset of articles, two coauthors independently determined final categories of definitions and independently assigned those categories.
 

Findings and implications

To define OA, Dr. DuMontier and colleagues used a cutoff of 60 years or older. Articles mentioning undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion (n = 256), but only 14 articles (5.5%) explicitly provided formal definitions.

For most of the reviewed articles, the authors judged definitions from the surrounding context. In a random subset of 50 articles, there was a high level of agreement (87.1%; κ = 0.81) between two coauthors in independently assigning categories of definitions.

Undertreatment was applied to therapy that was less than recommended (148 articles; 62.7%) or less than recommended with worse outcomes (88 articles; 37.3%).

Overtreatment most commonly denoted intensive treatment of an OA in whom harms outweighed the benefits of treatment (38 articles; 53.5%) or intensive treatment of a cancer not expected to affect the OA during the patient’s remaining life (33 articles; 46.5%).

Overall, the authors found that undertreatment and overtreatment of OAs with cancer are imprecisely defined concepts. Formal geriatric assessment was recommended in just over half of articles, and only 26.2% recommended formal assessments of age-related vulnerabilities for management. The authors proposed definitions that accounted for both oncologic factors and geriatric domains.
 

Care of individual patients and clinical research

National Comprehensive Cancer Network (NCCN) guidelines for OAs with cancer recommend initial consideration of overall life expectancy. If a patient is a candidate for cancer treatment on that basis, the next recommended assessment is that of the patient’s capacity to understand the relevant information, appreciate the underlying values and overall medical situation, reason through decisions, and communicate a choice that is consistent with the patient’s articulated goals.

In the pretreatment evaluation of OAs in whom there are no concerns about tolerance to antineoplastic therapy, NCCN guidelines suggest geriatric screening with standardized tools and, if abnormal, comprehensive geriatric screening. The guidelines recommend considering alternative treatment options if nonmodifiable abnormalities are identified.

Referral to a geriatric clinical specialist, use of the Cancer and Aging Research Group’s Chemo Toxicity Calculator, and calculation of Chemotherapy Risk Assessment Scale for High-Age Patients score are specifically suggested if high-risk procedures (such as chemotherapy, radiation, or complex surgery, which most oncologists would consider to be “another day in the office”) are contemplated.

The American Society of Clinical Oncology (ASCO) guidelines for geriatric oncology are similarly detailed and endorse similar evaluations and management.

Employing disease-centric and geriatric domains

Dr. DuMontier and colleagues noted that, for OAs with comorbidity or psychosocial challenges, surrogate survival endpoints are unrelated to quality of life (QOL) outcomes. Nonetheless, QOL is valued by OAs at least as much as survival improvement.

Through no fault of their own, the authors’ conclusion that undertreatment and overtreatment are imperfectly defined concepts has a certain neutrality to it. However, the terms undertreatment and overtreatment are commonly used to signify that inappropriate treatment decisions were made. Therefore, the terms are inherently negative and pejorative.

As with most emotionally charged issues in oncology, it is ideal for professionals in our field to take charge when deficiencies exist. ASCO, NCCN, and the authors of this scoping review have provided a conceptual basis for doing so.

An integrated oncologist-geriatrician approach was shown to be effective in the randomized INTEGERATE trial, showing improved QOL, reduced hospital admissions, and reduced early treatment discontinuation from adverse events (ASCO 2020, Abstract 12011).

Therefore, those clinicians who have not formally, systematically, and routinely supplemented the traditional disease-centric endpoints with patient-centered criteria need to do so.

Similarly, a retrospective study published in JAMA Network Open demonstrated that geriatric and surgical comanagement of OAs with cancer was associated with significantly lower 90-day postoperative mortality and receipt of more supportive care services (physical therapy, occupational therapy, speech and swallow rehabilitation, and nutrition services), in comparison with management from the surgical service only.

These clinical and administrative changes will not only enhance patient management but also facilitate the clinical trials required to clarify optimal treatment intensity. As that occurs, we will be able to apply as much precision to the care of OAs with cancer as we do in other areas of cancer treatment.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Dumontier C et al. J Clin Oncol. 2020 Aug 1;38(22):2558-2569.

Because of physiological changes with aging and differences in cancer biology, caring for older adults (OAs) with cancer requires careful assessment and planning.

Clark Dumontier, MD, of Brigham and Women’s Hospital in Boston, and colleagues sought to define the meaning of the terms “undertreatment” and “overtreatment” for OAs with cancer in a scoping literature review published in the Journal of Clinical Oncology.

Though OAs are typically defined as adults aged 65 years and older, in this review, the authors defined OAs as patients aged 60 years and older.

The authors theorized that a scoping review of papers about this patient population could provide clues about limitations in the oncology literature and guidance about patient management and future research. Despite comprising the majority of cancer patients, OAs are underrepresented in clinical trials.
 

About scoping reviews

Scoping reviews are used to identify existing evidence in a field, clarify concepts or definitions in the literature, survey how research on a topic is conducted, and identify knowledge gaps. In addition, scoping reviews summarize available evidence without answering a discrete research question.

Industry standards for scoping reviews have been established by the Johanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. According to these standards, scoping reviews should:

• Establish eligibility criteria with a rationale for each criterion clearly explained
• Search multiple databases in multiple languages
• Include “gray literature,” defined as studies that are unpublished or difficult to locate
• Have several independent reviewers screen titles and abstracts
• Ask multiple independent reviewers to review full text articles
• Present results with charts or diagrams that align with the review’s objective
• Graphically depict the decision process for including/excluding sources
• Identify implications for further research.

In their review, Dr. DuMontier and colleagues fulfilled many of the aforementioned criteria. The team searched three English-language databases for titles and abstracts that included the terms undertreatment and/or overtreatment, and were related to OAs with cancer, inclusive of all types of articles, cancer types, and treatments.

Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived. Within a random subset of articles, two coauthors independently determined final categories of definitions and independently assigned those categories.
 

Findings and implications

To define OA, Dr. DuMontier and colleagues used a cutoff of 60 years or older. Articles mentioning undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion (n = 256), but only 14 articles (5.5%) explicitly provided formal definitions.

For most of the reviewed articles, the authors judged definitions from the surrounding context. In a random subset of 50 articles, there was a high level of agreement (87.1%; κ = 0.81) between two coauthors in independently assigning categories of definitions.

Undertreatment was applied to therapy that was less than recommended (148 articles; 62.7%) or less than recommended with worse outcomes (88 articles; 37.3%).

Overtreatment most commonly denoted intensive treatment of an OA in whom harms outweighed the benefits of treatment (38 articles; 53.5%) or intensive treatment of a cancer not expected to affect the OA during the patient’s remaining life (33 articles; 46.5%).

Overall, the authors found that undertreatment and overtreatment of OAs with cancer are imprecisely defined concepts. Formal geriatric assessment was recommended in just over half of articles, and only 26.2% recommended formal assessments of age-related vulnerabilities for management. The authors proposed definitions that accounted for both oncologic factors and geriatric domains.
 

Care of individual patients and clinical research

National Comprehensive Cancer Network (NCCN) guidelines for OAs with cancer recommend initial consideration of overall life expectancy. If a patient is a candidate for cancer treatment on that basis, the next recommended assessment is that of the patient’s capacity to understand the relevant information, appreciate the underlying values and overall medical situation, reason through decisions, and communicate a choice that is consistent with the patient’s articulated goals.

In the pretreatment evaluation of OAs in whom there are no concerns about tolerance to antineoplastic therapy, NCCN guidelines suggest geriatric screening with standardized tools and, if abnormal, comprehensive geriatric screening. The guidelines recommend considering alternative treatment options if nonmodifiable abnormalities are identified.

Referral to a geriatric clinical specialist, use of the Cancer and Aging Research Group’s Chemo Toxicity Calculator, and calculation of Chemotherapy Risk Assessment Scale for High-Age Patients score are specifically suggested if high-risk procedures (such as chemotherapy, radiation, or complex surgery, which most oncologists would consider to be “another day in the office”) are contemplated.

The American Society of Clinical Oncology (ASCO) guidelines for geriatric oncology are similarly detailed and endorse similar evaluations and management.

Employing disease-centric and geriatric domains

Dr. DuMontier and colleagues noted that, for OAs with comorbidity or psychosocial challenges, surrogate survival endpoints are unrelated to quality of life (QOL) outcomes. Nonetheless, QOL is valued by OAs at least as much as survival improvement.

Through no fault of their own, the authors’ conclusion that undertreatment and overtreatment are imperfectly defined concepts has a certain neutrality to it. However, the terms undertreatment and overtreatment are commonly used to signify that inappropriate treatment decisions were made. Therefore, the terms are inherently negative and pejorative.

As with most emotionally charged issues in oncology, it is ideal for professionals in our field to take charge when deficiencies exist. ASCO, NCCN, and the authors of this scoping review have provided a conceptual basis for doing so.

An integrated oncologist-geriatrician approach was shown to be effective in the randomized INTEGERATE trial, showing improved QOL, reduced hospital admissions, and reduced early treatment discontinuation from adverse events (ASCO 2020, Abstract 12011).

Therefore, those clinicians who have not formally, systematically, and routinely supplemented the traditional disease-centric endpoints with patient-centered criteria need to do so.

Similarly, a retrospective study published in JAMA Network Open demonstrated that geriatric and surgical comanagement of OAs with cancer was associated with significantly lower 90-day postoperative mortality and receipt of more supportive care services (physical therapy, occupational therapy, speech and swallow rehabilitation, and nutrition services), in comparison with management from the surgical service only.

These clinical and administrative changes will not only enhance patient management but also facilitate the clinical trials required to clarify optimal treatment intensity. As that occurs, we will be able to apply as much precision to the care of OAs with cancer as we do in other areas of cancer treatment.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Dumontier C et al. J Clin Oncol. 2020 Aug 1;38(22):2558-2569.

Because of physiological changes with aging and differences in cancer biology, caring for older adults (OAs) with cancer requires careful assessment and planning.

Clark Dumontier, MD, of Brigham and Women’s Hospital in Boston, and colleagues sought to define the meaning of the terms “undertreatment” and “overtreatment” for OAs with cancer in a scoping literature review published in the Journal of Clinical Oncology.

Though OAs are typically defined as adults aged 65 years and older, in this review, the authors defined OAs as patients aged 60 years and older.

The authors theorized that a scoping review of papers about this patient population could provide clues about limitations in the oncology literature and guidance about patient management and future research. Despite comprising the majority of cancer patients, OAs are underrepresented in clinical trials.
 

About scoping reviews

Scoping reviews are used to identify existing evidence in a field, clarify concepts or definitions in the literature, survey how research on a topic is conducted, and identify knowledge gaps. In addition, scoping reviews summarize available evidence without answering a discrete research question.

Industry standards for scoping reviews have been established by the Johanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. According to these standards, scoping reviews should:

• Establish eligibility criteria with a rationale for each criterion clearly explained
• Search multiple databases in multiple languages
• Include “gray literature,” defined as studies that are unpublished or difficult to locate
• Have several independent reviewers screen titles and abstracts
• Ask multiple independent reviewers to review full text articles
• Present results with charts or diagrams that align with the review’s objective
• Graphically depict the decision process for including/excluding sources
• Identify implications for further research.

In their review, Dr. DuMontier and colleagues fulfilled many of the aforementioned criteria. The team searched three English-language databases for titles and abstracts that included the terms undertreatment and/or overtreatment, and were related to OAs with cancer, inclusive of all types of articles, cancer types, and treatments.

Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived. Within a random subset of articles, two coauthors independently determined final categories of definitions and independently assigned those categories.
 

Findings and implications

To define OA, Dr. DuMontier and colleagues used a cutoff of 60 years or older. Articles mentioning undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion (n = 256), but only 14 articles (5.5%) explicitly provided formal definitions.

For most of the reviewed articles, the authors judged definitions from the surrounding context. In a random subset of 50 articles, there was a high level of agreement (87.1%; κ = 0.81) between two coauthors in independently assigning categories of definitions.

Undertreatment was applied to therapy that was less than recommended (148 articles; 62.7%) or less than recommended with worse outcomes (88 articles; 37.3%).

Overtreatment most commonly denoted intensive treatment of an OA in whom harms outweighed the benefits of treatment (38 articles; 53.5%) or intensive treatment of a cancer not expected to affect the OA during the patient’s remaining life (33 articles; 46.5%).

Overall, the authors found that undertreatment and overtreatment of OAs with cancer are imprecisely defined concepts. Formal geriatric assessment was recommended in just over half of articles, and only 26.2% recommended formal assessments of age-related vulnerabilities for management. The authors proposed definitions that accounted for both oncologic factors and geriatric domains.
 

Care of individual patients and clinical research

National Comprehensive Cancer Network (NCCN) guidelines for OAs with cancer recommend initial consideration of overall life expectancy. If a patient is a candidate for cancer treatment on that basis, the next recommended assessment is that of the patient’s capacity to understand the relevant information, appreciate the underlying values and overall medical situation, reason through decisions, and communicate a choice that is consistent with the patient’s articulated goals.

In the pretreatment evaluation of OAs in whom there are no concerns about tolerance to antineoplastic therapy, NCCN guidelines suggest geriatric screening with standardized tools and, if abnormal, comprehensive geriatric screening. The guidelines recommend considering alternative treatment options if nonmodifiable abnormalities are identified.

Referral to a geriatric clinical specialist, use of the Cancer and Aging Research Group’s Chemo Toxicity Calculator, and calculation of Chemotherapy Risk Assessment Scale for High-Age Patients score are specifically suggested if high-risk procedures (such as chemotherapy, radiation, or complex surgery, which most oncologists would consider to be “another day in the office”) are contemplated.

The American Society of Clinical Oncology (ASCO) guidelines for geriatric oncology are similarly detailed and endorse similar evaluations and management.

Employing disease-centric and geriatric domains

Dr. DuMontier and colleagues noted that, for OAs with comorbidity or psychosocial challenges, surrogate survival endpoints are unrelated to quality of life (QOL) outcomes. Nonetheless, QOL is valued by OAs at least as much as survival improvement.

Through no fault of their own, the authors’ conclusion that undertreatment and overtreatment are imperfectly defined concepts has a certain neutrality to it. However, the terms undertreatment and overtreatment are commonly used to signify that inappropriate treatment decisions were made. Therefore, the terms are inherently negative and pejorative.

As with most emotionally charged issues in oncology, it is ideal for professionals in our field to take charge when deficiencies exist. ASCO, NCCN, and the authors of this scoping review have provided a conceptual basis for doing so.

An integrated oncologist-geriatrician approach was shown to be effective in the randomized INTEGERATE trial, showing improved QOL, reduced hospital admissions, and reduced early treatment discontinuation from adverse events (ASCO 2020, Abstract 12011).

Therefore, those clinicians who have not formally, systematically, and routinely supplemented the traditional disease-centric endpoints with patient-centered criteria need to do so.

Similarly, a retrospective study published in JAMA Network Open demonstrated that geriatric and surgical comanagement of OAs with cancer was associated with significantly lower 90-day postoperative mortality and receipt of more supportive care services (physical therapy, occupational therapy, speech and swallow rehabilitation, and nutrition services), in comparison with management from the surgical service only.

These clinical and administrative changes will not only enhance patient management but also facilitate the clinical trials required to clarify optimal treatment intensity. As that occurs, we will be able to apply as much precision to the care of OAs with cancer as we do in other areas of cancer treatment.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Dumontier C et al. J Clin Oncol. 2020 Aug 1;38(22):2558-2569.

Good news about cancer – with new data showing falling mortality rates and improved survival rates – is tempered somewhat by a “grim reality,” says the American Association for Cancer Research (AACR).

“The burden of cancer is not shouldered equally by all segments of the U.S. population,” the AACR adds. “The adverse differences in cancer burden that exist among certain population groups are one of the most pressing public health challenges that we face in the United States.” 

AACR president Antoni Ribas, MD, PhD, gave some examples of these disparities at a September 16 Congressional briefing that focused on the inaugural AACR Cancer Disparities Progress Report 2020.

He noted that:

• Black men have more than double the rate of death from prostate cancer compared with men of other racial and ethnic groups.
• Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.
• Non-Hispanic Black children and adolescents with cancer are more than 50% more likely to die from the cancer than non-Hispanic white children and adolescents with cancer.
• Women of low socioeconomic status with early stage ovarian cancer are 50% less likely to receive recommended care than are women of high socioeconomic status.
• In addition to racial and ethnic minority groups, other populations that bear a disproportionate burden when it comes to cancer include individuals lacking adequate health insurance coverage, immigrants, those with disabilities, residents in rural areas, and members of the lesbian, gay, bisexual, and transgender communities.

“It is absolutely unacceptable that advances in cancer care and treatment are not benefiting everyone equally,” Ribas commented.
 

Making progress against cancer

Progress being made against cancer was highlighted in another publication, the annual AACR Cancer Progress Report 2020.

U.S. cancer deaths declined by 29% between 1991 and 2017, translating to nearly 3 million cancer deaths avoided, the report notes. In addition, 5-year survival rates for all cancers combined increased from 49% in the mid-1970s to 70% for patients diagnosed from 2010-2016.

Between August 2019 and July 31 of this year, the U.S. Food and Drug Administration approved 20 new anticancer drugs for various cancer types and 15 new indications for previously approved cancer drugs, marking the highest number of approvals in one 12-month period since AACR started producing these reports 10 years ago.

A continuing reduction in the cigarette smoking rate among US adults, which is now below 14%, is contributing greatly to declines in lung cancer rates, which have largely driven the improvements in cancer survival, the AACR noted.

This report also notes that progress has been made toward reducing cancer disparities. Overall disparities in cancer death rates among racial and ethnic groups are less pronounced now than they have been in the past two decades. For example, the overall cancer death rate for African American patients was 33% higher than for White patients in 1990 but just 14% higher in 2016.

However, both reports agree that more must be done to reduce cancer disparities even further. 

They highlight initiatives that are underway, including:

• The draft guidance issued by the FDA to promote diversification of clinical trial populations.
• The National Institutes of Health’s (NIH’s) Continuing Umbrella of Research Experiences (CURE) program supporting underrepresented students and scientists along their academic and research career pathway.
• The Centers for Disease Control and Prevention’s Racial and Ethnic Approaches to Community Health (REACH) program, a grant-making program focused on encouraging preventive behaviors in underserved communities.
• The NIH’s All of Us program, which is gathering information from the genomes of 1 million healthy individuals with a focus on recruitment from historically underrepresented populations.

Ribas also announced that AACR has established a task force to focus on racial inequalities in cancer research.

Eliminating disparities would save money, argued John D. Carpten, PhD, from the University of Southern California, Los Angeles, who chaired the steering committee that developed the AACR Cancer Disparities Progress Report.

Carpten noted research showing that eliminating disparities for racial and ethnic minorities between 2003 and 2006 would have reduced health care costs by more than $1 trillion in the United States. This underscores the potentially far-reaching impact of efforts to eliminate disparities, he said.

“Without a doubt, socioeconomics and inequities in access to quality care represent major factors influencing cancer health disparities, and these disparities will persist until we address these issues” he said.

Both progress reports culminate in a call to action, largely focused on the need for “unwavering, bipartisan support from Congress, in the form of robust and sustained annual increases in funding for the NIH, NCI [National Cancer Institute], and FDA,” which is vital for accelerating the pace of progress.

The challenge is now compounded by the ongoing COVID-19 pandemic: Both progress reports note that racial and ethnic minorities, including African Americans, are not only affected disproportionately by cancer, but also by COVID-19, further highlighting the “stark inequities in health care.”

Ribas further called for action from national leadership and the scientific community.

“During this unprecedented time in our nation’s history, there is also a need for our nation’s leaders to take on a much bigger role in confronting and combating the structural and systemic racism that contributes to health disparities,” he said. The “pervasive racism and social injustices” that have contributed to disparities in both COVID-19 and cancer underscore the need for “the scientific community to step up and partner with Congress to assess and address this issue within the research community.”

This article first appeared on Medscape.com.

Good news about cancer – with new data showing falling mortality rates and improved survival rates – is tempered somewhat by a “grim reality,” says the American Association for Cancer Research (AACR).

“The burden of cancer is not shouldered equally by all segments of the U.S. population,” the AACR adds. “The adverse differences in cancer burden that exist among certain population groups are one of the most pressing public health challenges that we face in the United States.” 

AACR president Antoni Ribas, MD, PhD, gave some examples of these disparities at a September 16 Congressional briefing that focused on the inaugural AACR Cancer Disparities Progress Report 2020.

He noted that:

• Black men have more than double the rate of death from prostate cancer compared with men of other racial and ethnic groups.
• Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.
• Non-Hispanic Black children and adolescents with cancer are more than 50% more likely to die from the cancer than non-Hispanic white children and adolescents with cancer.
• Women of low socioeconomic status with early stage ovarian cancer are 50% less likely to receive recommended care than are women of high socioeconomic status.
• In addition to racial and ethnic minority groups, other populations that bear a disproportionate burden when it comes to cancer include individuals lacking adequate health insurance coverage, immigrants, those with disabilities, residents in rural areas, and members of the lesbian, gay, bisexual, and transgender communities.

“It is absolutely unacceptable that advances in cancer care and treatment are not benefiting everyone equally,” Ribas commented.
 

Making progress against cancer

Progress being made against cancer was highlighted in another publication, the annual AACR Cancer Progress Report 2020.

U.S. cancer deaths declined by 29% between 1991 and 2017, translating to nearly 3 million cancer deaths avoided, the report notes. In addition, 5-year survival rates for all cancers combined increased from 49% in the mid-1970s to 70% for patients diagnosed from 2010-2016.

Between August 2019 and July 31 of this year, the U.S. Food and Drug Administration approved 20 new anticancer drugs for various cancer types and 15 new indications for previously approved cancer drugs, marking the highest number of approvals in one 12-month period since AACR started producing these reports 10 years ago.

A continuing reduction in the cigarette smoking rate among US adults, which is now below 14%, is contributing greatly to declines in lung cancer rates, which have largely driven the improvements in cancer survival, the AACR noted.

This report also notes that progress has been made toward reducing cancer disparities. Overall disparities in cancer death rates among racial and ethnic groups are less pronounced now than they have been in the past two decades. For example, the overall cancer death rate for African American patients was 33% higher than for White patients in 1990 but just 14% higher in 2016.

However, both reports agree that more must be done to reduce cancer disparities even further. 

They highlight initiatives that are underway, including:

• The draft guidance issued by the FDA to promote diversification of clinical trial populations.
• The National Institutes of Health’s (NIH’s) Continuing Umbrella of Research Experiences (CURE) program supporting underrepresented students and scientists along their academic and research career pathway.
• The Centers for Disease Control and Prevention’s Racial and Ethnic Approaches to Community Health (REACH) program, a grant-making program focused on encouraging preventive behaviors in underserved communities.
• The NIH’s All of Us program, which is gathering information from the genomes of 1 million healthy individuals with a focus on recruitment from historically underrepresented populations.

Ribas also announced that AACR has established a task force to focus on racial inequalities in cancer research.

Eliminating disparities would save money, argued John D. Carpten, PhD, from the University of Southern California, Los Angeles, who chaired the steering committee that developed the AACR Cancer Disparities Progress Report.

Carpten noted research showing that eliminating disparities for racial and ethnic minorities between 2003 and 2006 would have reduced health care costs by more than $1 trillion in the United States. This underscores the potentially far-reaching impact of efforts to eliminate disparities, he said.

“Without a doubt, socioeconomics and inequities in access to quality care represent major factors influencing cancer health disparities, and these disparities will persist until we address these issues” he said.

Both progress reports culminate in a call to action, largely focused on the need for “unwavering, bipartisan support from Congress, in the form of robust and sustained annual increases in funding for the NIH, NCI [National Cancer Institute], and FDA,” which is vital for accelerating the pace of progress.

The challenge is now compounded by the ongoing COVID-19 pandemic: Both progress reports note that racial and ethnic minorities, including African Americans, are not only affected disproportionately by cancer, but also by COVID-19, further highlighting the “stark inequities in health care.”

Ribas further called for action from national leadership and the scientific community.

“During this unprecedented time in our nation’s history, there is also a need for our nation’s leaders to take on a much bigger role in confronting and combating the structural and systemic racism that contributes to health disparities,” he said. The “pervasive racism and social injustices” that have contributed to disparities in both COVID-19 and cancer underscore the need for “the scientific community to step up and partner with Congress to assess and address this issue within the research community.”

This article first appeared on Medscape.com.

Good news about cancer – with new data showing falling mortality rates and improved survival rates – is tempered somewhat by a “grim reality,” says the American Association for Cancer Research (AACR).

“The burden of cancer is not shouldered equally by all segments of the U.S. population,” the AACR adds. “The adverse differences in cancer burden that exist among certain population groups are one of the most pressing public health challenges that we face in the United States.” 

AACR president Antoni Ribas, MD, PhD, gave some examples of these disparities at a September 16 Congressional briefing that focused on the inaugural AACR Cancer Disparities Progress Report 2020.

He noted that:

• Black men have more than double the rate of death from prostate cancer compared with men of other racial and ethnic groups.
• Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.
• Non-Hispanic Black children and adolescents with cancer are more than 50% more likely to die from the cancer than non-Hispanic white children and adolescents with cancer.
• Women of low socioeconomic status with early stage ovarian cancer are 50% less likely to receive recommended care than are women of high socioeconomic status.
• In addition to racial and ethnic minority groups, other populations that bear a disproportionate burden when it comes to cancer include individuals lacking adequate health insurance coverage, immigrants, those with disabilities, residents in rural areas, and members of the lesbian, gay, bisexual, and transgender communities.

“It is absolutely unacceptable that advances in cancer care and treatment are not benefiting everyone equally,” Ribas commented.
 

Making progress against cancer

Progress being made against cancer was highlighted in another publication, the annual AACR Cancer Progress Report 2020.

U.S. cancer deaths declined by 29% between 1991 and 2017, translating to nearly 3 million cancer deaths avoided, the report notes. In addition, 5-year survival rates for all cancers combined increased from 49% in the mid-1970s to 70% for patients diagnosed from 2010-2016.

Between August 2019 and July 31 of this year, the U.S. Food and Drug Administration approved 20 new anticancer drugs for various cancer types and 15 new indications for previously approved cancer drugs, marking the highest number of approvals in one 12-month period since AACR started producing these reports 10 years ago.

A continuing reduction in the cigarette smoking rate among US adults, which is now below 14%, is contributing greatly to declines in lung cancer rates, which have largely driven the improvements in cancer survival, the AACR noted.

This report also notes that progress has been made toward reducing cancer disparities. Overall disparities in cancer death rates among racial and ethnic groups are less pronounced now than they have been in the past two decades. For example, the overall cancer death rate for African American patients was 33% higher than for White patients in 1990 but just 14% higher in 2016.

However, both reports agree that more must be done to reduce cancer disparities even further. 

They highlight initiatives that are underway, including:

• The draft guidance issued by the FDA to promote diversification of clinical trial populations.
• The National Institutes of Health’s (NIH’s) Continuing Umbrella of Research Experiences (CURE) program supporting underrepresented students and scientists along their academic and research career pathway.
• The Centers for Disease Control and Prevention’s Racial and Ethnic Approaches to Community Health (REACH) program, a grant-making program focused on encouraging preventive behaviors in underserved communities.
• The NIH’s All of Us program, which is gathering information from the genomes of 1 million healthy individuals with a focus on recruitment from historically underrepresented populations.

Ribas also announced that AACR has established a task force to focus on racial inequalities in cancer research.

Eliminating disparities would save money, argued John D. Carpten, PhD, from the University of Southern California, Los Angeles, who chaired the steering committee that developed the AACR Cancer Disparities Progress Report.

Carpten noted research showing that eliminating disparities for racial and ethnic minorities between 2003 and 2006 would have reduced health care costs by more than $1 trillion in the United States. This underscores the potentially far-reaching impact of efforts to eliminate disparities, he said.

“Without a doubt, socioeconomics and inequities in access to quality care represent major factors influencing cancer health disparities, and these disparities will persist until we address these issues” he said.

Both progress reports culminate in a call to action, largely focused on the need for “unwavering, bipartisan support from Congress, in the form of robust and sustained annual increases in funding for the NIH, NCI [National Cancer Institute], and FDA,” which is vital for accelerating the pace of progress.

The challenge is now compounded by the ongoing COVID-19 pandemic: Both progress reports note that racial and ethnic minorities, including African Americans, are not only affected disproportionately by cancer, but also by COVID-19, further highlighting the “stark inequities in health care.”

Ribas further called for action from national leadership and the scientific community.

“During this unprecedented time in our nation’s history, there is also a need for our nation’s leaders to take on a much bigger role in confronting and combating the structural and systemic racism that contributes to health disparities,” he said. The “pervasive racism and social injustices” that have contributed to disparities in both COVID-19 and cancer underscore the need for “the scientific community to step up and partner with Congress to assess and address this issue within the research community.”

This article first appeared on Medscape.com.

For patients with multiple myeloma, triplet induction with novel agents beat doublet with regards to early results, according to Lalit Kumar, MD, and colleagues at the All India Institute of Medical sciences Myeloma Group, New Delhi.

The study analyzed 326 multiple myeloma patients who received high-dose, novel agent–based induction therapy prior to autologous stem cell transplant (ASCT) at a single institution, according to a report published in Clinical Lymphoma, Myeloma and Leukemia.

Between January 2005 and December 2018, 326 consecutive patients underwent high-dose chemotherapy and autologous stem cell transplant. The median age of the patients was 52 years; 66% were men, nearly 33% had Revised ISS III disease; almost 16% had high-risk cytogenetics and 23% underwent transplant in second remission after salvage therapy for relapse. A total of 194 patients (59.5%) received induction with two novel agents (thalidomide/dexamethasone, n = 95; lenalidomide/dexamethasone, n = 63; bortezomib/dexamethasone, n = 36) and 132 (40.5%) received three drugs (bortezomib/lenalidomide/dexamethasone, n = 53; bortezomib/liposomal doxorubicin/dexamethasone, n = 42; bortezomib/thalidomide/dexamethasone, n = 31; other n = 3).
 

Outcomes favorable

After transplant 227 (69.8%) patients achieved a complete response; 48 (14.7%) had a very good partial response, 32 (9.8%) had a partial response, and 9 (2.8%) patients had stable disease. Ten (3.1%) patients died of transplant-related complications (before day 100). Triplet induction beat doublet with regards to early response (95.4% vs. 84.02% [doublets], P < .003), stem cell mobilization (88.6% vs. 76.8%, P < .005) and lower day-100 transplant-related mortality (P < .001), However, at a median follow-up of 62.5 months, the median overall response rate (97.5 months triplet vs. 100.0 months doublet) and the median progression free survival (54.5 months vs. 57 months) were not statistically different between the two induction-treatment groups.

Patients who had undergone transplant in a recent period (2016-18) had a better outcome, compared with initial years, which possibly reflects a combined effect of learning curve, use of triplets, and gradual reduction in day-100 mortality, the authors stated.

“Whether newer regimens incorporating monoclonal antibodies (associated with higher [complete response] rate and [minimal residual disease] negativity) would result in further improvement in survival, needs to be determined in future studies,” the researchers concluded.

The authors reported that they had no conflicts.

[email protected]

SOURCE: Kumar L et al. Clin Lymphoma Myeloma Leuk. 2020 Sep 18. doi: 10.1016/j.clml.2020.08.021.

For patients with multiple myeloma, triplet induction with novel agents beat doublet with regards to early results, according to Lalit Kumar, MD, and colleagues at the All India Institute of Medical sciences Myeloma Group, New Delhi.

The study analyzed 326 multiple myeloma patients who received high-dose, novel agent–based induction therapy prior to autologous stem cell transplant (ASCT) at a single institution, according to a report published in Clinical Lymphoma, Myeloma and Leukemia.

Between January 2005 and December 2018, 326 consecutive patients underwent high-dose chemotherapy and autologous stem cell transplant. The median age of the patients was 52 years; 66% were men, nearly 33% had Revised ISS III disease; almost 16% had high-risk cytogenetics and 23% underwent transplant in second remission after salvage therapy for relapse. A total of 194 patients (59.5%) received induction with two novel agents (thalidomide/dexamethasone, n = 95; lenalidomide/dexamethasone, n = 63; bortezomib/dexamethasone, n = 36) and 132 (40.5%) received three drugs (bortezomib/lenalidomide/dexamethasone, n = 53; bortezomib/liposomal doxorubicin/dexamethasone, n = 42; bortezomib/thalidomide/dexamethasone, n = 31; other n = 3).
 

Outcomes favorable

After transplant 227 (69.8%) patients achieved a complete response; 48 (14.7%) had a very good partial response, 32 (9.8%) had a partial response, and 9 (2.8%) patients had stable disease. Ten (3.1%) patients died of transplant-related complications (before day 100). Triplet induction beat doublet with regards to early response (95.4% vs. 84.02% [doublets], P < .003), stem cell mobilization (88.6% vs. 76.8%, P < .005) and lower day-100 transplant-related mortality (P < .001), However, at a median follow-up of 62.5 months, the median overall response rate (97.5 months triplet vs. 100.0 months doublet) and the median progression free survival (54.5 months vs. 57 months) were not statistically different between the two induction-treatment groups.

Patients who had undergone transplant in a recent period (2016-18) had a better outcome, compared with initial years, which possibly reflects a combined effect of learning curve, use of triplets, and gradual reduction in day-100 mortality, the authors stated.

“Whether newer regimens incorporating monoclonal antibodies (associated with higher [complete response] rate and [minimal residual disease] negativity) would result in further improvement in survival, needs to be determined in future studies,” the researchers concluded.

The authors reported that they had no conflicts.

[email protected]

SOURCE: Kumar L et al. Clin Lymphoma Myeloma Leuk. 2020 Sep 18. doi: 10.1016/j.clml.2020.08.021.

For patients with multiple myeloma, triplet induction with novel agents beat doublet with regards to early results, according to Lalit Kumar, MD, and colleagues at the All India Institute of Medical sciences Myeloma Group, New Delhi.

The study analyzed 326 multiple myeloma patients who received high-dose, novel agent–based induction therapy prior to autologous stem cell transplant (ASCT) at a single institution, according to a report published in Clinical Lymphoma, Myeloma and Leukemia.

Between January 2005 and December 2018, 326 consecutive patients underwent high-dose chemotherapy and autologous stem cell transplant. The median age of the patients was 52 years; 66% were men, nearly 33% had Revised ISS III disease; almost 16% had high-risk cytogenetics and 23% underwent transplant in second remission after salvage therapy for relapse. A total of 194 patients (59.5%) received induction with two novel agents (thalidomide/dexamethasone, n = 95; lenalidomide/dexamethasone, n = 63; bortezomib/dexamethasone, n = 36) and 132 (40.5%) received three drugs (bortezomib/lenalidomide/dexamethasone, n = 53; bortezomib/liposomal doxorubicin/dexamethasone, n = 42; bortezomib/thalidomide/dexamethasone, n = 31; other n = 3).
 

Outcomes favorable

After transplant 227 (69.8%) patients achieved a complete response; 48 (14.7%) had a very good partial response, 32 (9.8%) had a partial response, and 9 (2.8%) patients had stable disease. Ten (3.1%) patients died of transplant-related complications (before day 100). Triplet induction beat doublet with regards to early response (95.4% vs. 84.02% [doublets], P < .003), stem cell mobilization (88.6% vs. 76.8%, P < .005) and lower day-100 transplant-related mortality (P < .001), However, at a median follow-up of 62.5 months, the median overall response rate (97.5 months triplet vs. 100.0 months doublet) and the median progression free survival (54.5 months vs. 57 months) were not statistically different between the two induction-treatment groups.

Patients who had undergone transplant in a recent period (2016-18) had a better outcome, compared with initial years, which possibly reflects a combined effect of learning curve, use of triplets, and gradual reduction in day-100 mortality, the authors stated.

“Whether newer regimens incorporating monoclonal antibodies (associated with higher [complete response] rate and [minimal residual disease] negativity) would result in further improvement in survival, needs to be determined in future studies,” the researchers concluded.

The authors reported that they had no conflicts.

[email protected]

SOURCE: Kumar L et al. Clin Lymphoma Myeloma Leuk. 2020 Sep 18. doi: 10.1016/j.clml.2020.08.021.

Two new protein biomarkers may serve as prognostic indicators for outcomes in chronic lymphocytic leukemia (CLL) patients, according to the results of a proteomic assessment of patients’ serum compared to their event-free survival (EFS).

The results were published in Experimental Hematology.

The study attempted to validate the prognostic ability of known proteomic markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL, according to Fatemeh Saberi Hosnijeh, MD, of Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and colleagues.

Baseline serum samples were taken from 51 CLL patients who were then treated with chemoimmunotherapy. The samples were analyzed for 360 proteomic markers, and those results were compared with patient EFS.

Study subjects were selected from patients enrolled in the HOVON 109 clinical trial, a phase 1/2 trial designed to assess the efficacy and safety of first-line therapy involving chlorambucil, rituximab,and lenalidomide in elderly patients and young frail patients with advanced CLL.

The patients assessed comprised 30 men and 21 women, and the median EFS for all patients was 23 months (ranging from 1.25 to 60.9 months).
 

Promising biomarkers

The researchers found that patients who had high serum levels of the proteins sCD23 (P = .026), sCD27 (P = .04), the serine peptidase inhibitor SPINT1 (P = .001), and the surface antigen protein LY9 (P = .0003) had a shorter EFS than those with marker levels below the median.

“Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients,” the researchers stated.

“Despite the relatively small number of available cases, which had an impact on statistical power, our pilot study identified SPINT1 and LY9 as promising independent prognostic proteomic markers next to sCD23 and sCD27 in patients treated for CLL. Further studies with larger sample sizes are required to validate these results,” the researchers concluded.

This research was supported by a grant from Gilead Sciences and an EU TRANSCAN/Dutch Cancer Society grant. The authors declared that they had no conflicts of interest.

[email protected]

SOURCE: Hosnijeh FS et al. Exp Hematol. 2020;89:55-60.

Two new protein biomarkers may serve as prognostic indicators for outcomes in chronic lymphocytic leukemia (CLL) patients, according to the results of a proteomic assessment of patients’ serum compared to their event-free survival (EFS).

The results were published in Experimental Hematology.

The study attempted to validate the prognostic ability of known proteomic markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL, according to Fatemeh Saberi Hosnijeh, MD, of Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and colleagues.

Baseline serum samples were taken from 51 CLL patients who were then treated with chemoimmunotherapy. The samples were analyzed for 360 proteomic markers, and those results were compared with patient EFS.

Study subjects were selected from patients enrolled in the HOVON 109 clinical trial, a phase 1/2 trial designed to assess the efficacy and safety of first-line therapy involving chlorambucil, rituximab,and lenalidomide in elderly patients and young frail patients with advanced CLL.

The patients assessed comprised 30 men and 21 women, and the median EFS for all patients was 23 months (ranging from 1.25 to 60.9 months).
 

Promising biomarkers

The researchers found that patients who had high serum levels of the proteins sCD23 (P = .026), sCD27 (P = .04), the serine peptidase inhibitor SPINT1 (P = .001), and the surface antigen protein LY9 (P = .0003) had a shorter EFS than those with marker levels below the median.

“Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients,” the researchers stated.

“Despite the relatively small number of available cases, which had an impact on statistical power, our pilot study identified SPINT1 and LY9 as promising independent prognostic proteomic markers next to sCD23 and sCD27 in patients treated for CLL. Further studies with larger sample sizes are required to validate these results,” the researchers concluded.

This research was supported by a grant from Gilead Sciences and an EU TRANSCAN/Dutch Cancer Society grant. The authors declared that they had no conflicts of interest.

[email protected]

SOURCE: Hosnijeh FS et al. Exp Hematol. 2020;89:55-60.

Two new protein biomarkers may serve as prognostic indicators for outcomes in chronic lymphocytic leukemia (CLL) patients, according to the results of a proteomic assessment of patients’ serum compared to their event-free survival (EFS).

The results were published in Experimental Hematology.

The study attempted to validate the prognostic ability of known proteomic markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL, according to Fatemeh Saberi Hosnijeh, MD, of Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and colleagues.

Baseline serum samples were taken from 51 CLL patients who were then treated with chemoimmunotherapy. The samples were analyzed for 360 proteomic markers, and those results were compared with patient EFS.

Study subjects were selected from patients enrolled in the HOVON 109 clinical trial, a phase 1/2 trial designed to assess the efficacy and safety of first-line therapy involving chlorambucil, rituximab,and lenalidomide in elderly patients and young frail patients with advanced CLL.

The patients assessed comprised 30 men and 21 women, and the median EFS for all patients was 23 months (ranging from 1.25 to 60.9 months).
 

Promising biomarkers

The researchers found that patients who had high serum levels of the proteins sCD23 (P = .026), sCD27 (P = .04), the serine peptidase inhibitor SPINT1 (P = .001), and the surface antigen protein LY9 (P = .0003) had a shorter EFS than those with marker levels below the median.

“Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients,” the researchers stated.

“Despite the relatively small number of available cases, which had an impact on statistical power, our pilot study identified SPINT1 and LY9 as promising independent prognostic proteomic markers next to sCD23 and sCD27 in patients treated for CLL. Further studies with larger sample sizes are required to validate these results,” the researchers concluded.

This research was supported by a grant from Gilead Sciences and an EU TRANSCAN/Dutch Cancer Society grant. The authors declared that they had no conflicts of interest.

[email protected]

SOURCE: Hosnijeh FS et al. Exp Hematol. 2020;89:55-60.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.