Abstract IA28: Disparities in late effects incidence among adolescent and young survivors of lymphoma
Authors: Li Qian W. , Brunson Ann , Wun Ted , Abrahao Renata , Keegan Theresa H. M. 
Published: December 2020

Background: Survival after lymphomas, the most common malignancies in adolescents and young adults (AYAs), has improved significantly over time as a result of advances in diagnostic procedures and therapeutic management. However, studies have shown that survival varies substantially by race/ethnicity, socioeconomic status (SES), health insurance coverage, and clinical factors. Additionally, therapies that lead to cure, such as chemotherapy and radiation, can result in an elevated lifetime risk of chronic medical conditions (“late effects”) that can considerably impair the quality of life and increase mortality of survivors. We aimed to estimate the burden of late effects in AYA lymphomas survivors and identify sociodemographic and clinical factors associated with late effects incidence.

Methods: We used data from the California Cancer Registry linked to hospitalization data from the California Office Statewide Health Planning and Development. Eligible patients were those diagnosed with a first primary non-Hodgkin (NHL) or Hodgkin lymphoma (HL) from 1996 to 2012 who survived at least 2 years after diagnosis. Patients were followed through 2014. The late effects included cardiovascular, respiratory, kidney, liver, endocrine, and neurologic diseases, as well as avascular necrosis and second cancers. We estimated the cumulative incidence of each condition, accounting for death as a competing risk. Cox proportional hazards regression models were used to examine the relation of sociodemographic and clinical factors to late effects, providing an estimate of the hazard ratio (HR) and associated 95% confidence intervals (CI). NHL and HL models were adjusted for age at diagnosis, year of diagnosis, stage at diagnosis, sex, race/ethnicity, cancer subtype (NHL), B-symptoms (HL), initial treatment (chemotherapy and radiation), receipt of a hematopoietic stem cell transplant (HSCT), health insurance, and neighborhood SES. Patients with human immunodeficiency virus (HIV) infection were considered separately in the NHL analyses and excluded from the HL analyses.

Results: We identified 5,085 HL and 4,817 NHL survivors. Of those with NHL, 425 (9%) were HIV infected. In both HL and NHL cohorts, the highest cumulative incidence of late effects was observed for endocrine, cardiovascular, and respiratory diseases. Among NHL survivors, those with HIV infection had a higher incidence of all late effects, including an over 3-fold higher risk of second cancers compared with HIV-uninfected survivors (8.1% vs. 2.6%, respectively). We observed that, except for hypothyroidism, HL patients diagnosed with late (vs. early) stage disease had a greater incidence of all late effects. In multivariable adjusted models, HL survivors who underwent an HSCT experienced 1.7 to 3.4-fold higher risk of all late effects than non-HSCT recipients. Similarly, among HIV-uninfected NHL survivors, those who underwent an HSCT had a higher risk of most late effects, particularly avascular necrosis (HR=4.6, 95% CI 2.4–8.8). Except for second cancers, uninsured/publicly insured HL survivors experienced a 1.3–1.8 greater risk of all late effects compared with those with private insurance. For NHL, AYAs with public/no insurance had 1.6 to 2.4 higher risk of several late effects, particularly neurologic diseases (HR=2.4, 95% CI 1.5–3.8). Additionally, we observed that HL and NHL patients who lived in lower SES neighborhoods had a higher risk of respiratory and endocrine diseases and NHL survivors living in lower SES neighborhoods also had a higher risk of cardiovascular diseases. Compared to non-Hispanic whites, Black HL survivors were more likely to have cardiovascular diseases, and Black and Hispanic survivors were more likely to have endocrine diseases. Furthermore, among NHL survivors, Hispanics experienced a 73% and Blacks a 91% greater risk of renal diseases. Differences by race/ethnicity were more pronounced among NHL survivors with HIV infection, with those of non-white race/ethnicity experiencing a nearly 6-fold higher risk of renal diseases. Importantly, HL AYA survivors who experienced any late effect had an over 2-fold increased risk of death (HR=2.1–6.2).

Conclusion: To our knowledge, this is the first US population-based study to examine the influence of sociodemographic factors on the incidence of late effects, as well as to compare the risk between NHL HIV-infected vs. HIV-uninfected survivors. We found substantial incidence of late effects in AYA survivors of both NHL and HL in California and identified populations with a higher incidence of these conditions. Specifically, we found that AYA survivors of Black or Hispanic race/ethnicity, those who had public or no health insurance, who underwent a HSCT, or resided in lower SES neighborhoods were consistently at higher risk of developing late effects. In addition, NHL survivors with HIV infection had a strikingly greater risk of all conditions. These sociodemographic and clinical factors have been associated with worse survival among AYAs. In order to improve outcomes and reduce health disparities in these young cancer survivors, our findings highlight the critical need to address these late effects by increasing education of AYAs on their risks and the importance of survivorship care and reducing health insurance and financial barriers to receiving quality care.

Citation Format: Qian W. Li, Ann Brunson, Ted Wun, Renata Abrahao, Theresa H. M. Keegan. Disparities in late effects incidence among adolescent and young survivors of lymphoma [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr IA28.