The late effects of adolescent and young adults (AYA) with lymphomas are considerable and have not been given much attention, according to Theresa Keegan, MD, of the University of California at Davis.
“Lymphoma is one of the most commonly occurring malignancies in AYAs,” she stated. “The 5-year survival of AYAs with Hodgkin lymphoma [HL] is 95% and for non-HL [NHL] is 78% among AYAs diagnosed between 2002 to 2006. Despite this improvement in survival, population-based studies have documented disparities in survival by race/ethnicity, neighborhood socioeconomic status, and insurance type, with worse survival associated with lower socioeconomic status,” Dr. Keegan told listeners during the 2020 American Association for Cancer Research (AACR) Virtual Meeting: Advances in Malignant Lymphoma.1
“This is one of the first U.S. population–based studies to examine socioeconomic disparities in the incidence of late effects, as well as to compare risks between HIV-infected vs HIV-uninfected survivors of NHL.”— Theresa Keegan, MD
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Studies that have considered these factors show that AYA cancer survivors have a lifelong elevated risk of chronic medical conditions and second cancers as a result of curative cancer therapy. They include endocrine, respiratory, renal, liver, and cardiovascular disease.
In fact, in a large insured population, the prevalence of multiple comorbidities approaches 40% at 12 years after diagnosis, nearly twice as much as age-matched controls.2 The risk of cardiovascular disease was 2.8-fold higher than in comparison patients without cancer, and those who developed cardiovascular disease had an 11-fold increase in death from all causes.
The incidence of cardiovascular disease in AYA cancer survivors increases with decreasing socioeconomic status. Patients who are uninsured at diagnosis have a substantially increased risk, and Black individuals had the highest incidence of cardiovascular disease.
Population-Based Study Findings
“Few population-based studies have looked at socioeconomic factors and their association with late effects in AYAs,” noted Dr. Keegan.
She reported on results of a population-based study of a range of late effects and their association with sociodemographic and clinical factors among AYA survivors of HL and NHL in California. Participants were drawn from two large databases—California Cancer Registry and hospitalization data from the Office of Statewide Hospital Planning and Development from 1996 to 2012.3 “We believe our findings will help us identify patients with a higher risk of poor outcomes and inform strategies to improve surveillance and patient care,” Dr. Keegan stated.
“This was a diverse population. Among 425 HIV-infected NHL survivors, they were more likely to be diagnosed with advanced-stage cancer, have a lower socioeconomic status, and were less likely to have private health insurance than NHL survivors without HIV and HL survivors,” reported Dr. Keegan.
In the NHL cohort, the 10-year cumulative incidence of all late effects was higher in NHL survivors living with HIV than in those who were not infected with HIV. The most common late effects in the NHL cohort included (in descending order) endocrine, cardiovascular, and respiratory effects.
Among the HL cohort, the most common late effects were also cardiovascular, respiratory, and endocrine diseases. With the exception of hypothyroidism, the incidence of late effects was higher among patients with HL diagnosed at a more advanced stage disease.
Other Clinical Factors
In a multivariate analysis of NHL survivors without HIV, hematopoietic stem cell transplantation was associated with cardiovascular, respiratory, renal, and endocrine diseases, as well as avascular necrosis. In patients with HL, hematopoietic stem cell transplantation was associated with a higher risk of all late effects considered.3
With the exception of second cancers and avascular necrosis, public or no health insurance was associated with a higher risk of late effects in HIV-infected NHL survivors, and this was similar (except for second cancers) for HL survivors.3 Lower socioeconomic status was associated with a higher risk of cardiovascular, respiratory, and endocrine diseases among non-infected survivors of NHL and a higher risk of respiratory disease in HL survivors.
Looking at race/ethnicity among NHL survivors, Hispanic and Black survivors had a higher risk of renal disease than did non-Hispanic Whites. Among HL survivors, Black survivors were more likely to have cardiovascular disease, and Black and Hispanic survivors were more likely to have endocrine diseases than were non-Hispanic Whites.3
Mortality was increased in HL survivors with late effects. In an adjusted analysis, overall survival was two to six times poorer for HL survivors with various late effects. In addition, HL-specific survival was two to eight times worse.3
“Although the study had several limitations, our findings are likely to be generalizable to survivors of AYA lymphomas, as we have included a large, diverse population of AYAs and those who received care across all types of institutions,” noted Dr. Keegan.
Strategies to Address Disparities
“The care of those with cancer involves a continuum. Survivors require surveillance and management of physical and psychosocial effects, prevention and surveillance for second cancers, health promotion, as well as surveillance and management of late effects,” Dr. Keegan stated.
“This is one of the first U.S. population–based studies to examine socioeconomic disparities in the incidence of late effects, as well as to compare risks between HIV-infected vs HIV-uninfected survivors of NHL. We found a substantial incidence of late effects following lymphomas in AYAs, particularly cardiovascular, endocrine, and respiratory diseases, as well as second cancers. We were able to identify AYAs at a higher risk of late effects, including those with HIV and those who underwent hematopoietic stem cell transplantation,” Dr. Keegan stated.
“We see consistently higher late effects among those with no/public insurance. Our health insurance findings may relate to reduced access to preventive care, early detection/intervention, or long-term surveillance,” continued Dr. Keegan. “Socioeconomic status findings may relate to the financial impact of cancer. Survivors are often faced with large medical bills and may have low work ability or may be unemployed. AYA survivors are more likely to forgo care due to cost barriers.”
Dr. Keegan ended her presentation by emphasizing the importance of education for AYAs and providers on their risk of late effects and the importance of survivorship care.
DISCLOSURE: Dr. Keegan has received institutional research funding from Shire.
1. Keegan TH: Disparities in late effects incidence among adolescent and young survivors of lymphoma. 2020 AACR Virtual Meeting: Advances in Malignant Lymphoma. Presented August 14, 2020.
2. Chao C, Bhatia S, Xu L, et al: Chronic comorbidities among survivors of adolescent and young adult cancer. J Clin Oncol. July 16, 2020 (early release online).
3. Keegan THM, Li Q, Steele A, et al: Socioeconomic disparities in the occurrence of medical conditions among adolescent and young adult Hodgkin lymphoma survivors. Cancer Causes Control 29:551-561, 2018.
Christopher Flowers, MD
Commenting on this presentation, session moderator Christopher Flowers, MD, Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, Houston, said: “The treatment of adolescent and young adult patients with lymphoma remains a...