Survival after Diffuse Large B-Cell Lymphoma Among Children, Adolescents and Young Adults in the Era of Immunotherapy: A Population-Based Study

Abstract

Introduction Diffuse large B-cell lymphoma (DLBCL) is the most frequent non-Hodgkin lymphoma in adolescents and young adults (AYAs, 20-39 years [y]) and the third most common in children (0-19y). Data on outcomes for AYAs with DLBCL are scarce, but substantial survival gap has been reported, with children having better survival than AYAs, even in the modern era of treatment with immunotherapy combined with conventional chemotherapy. We aimed to investigate the influence of rituximab on the survival of children and AYAs with DLBCL in California.Methods We obtained data from the Greater Bay Area Cancer Registry, which covers 9 California counties and captures at least 98% of all cancer cases. Eligible cases were patients aged less than 39 years when diagnosed with DLBCL during 2001-2014. Facility-level reports for each patient were reviewed in order to abstract information on treatment regimens. Kaplan Meier method was used to estimate 5-year overall survival (OS). Cox proportional regression models were performed to examine the association between OS and treatment, adjusted for age at diagnosis, gender, stage at diagnosis, health insurance status, treatment facility (whether associated with NCI-designated cancer [NCIDCC]), race/ethnicity (including non-Hispanic whites [NHW], non-Hispanic blacks, Hispanics, and Asians/Pacific Islanders [API]), neighborhood socioeconomic status (nSES), and year of diagnosis. Results are presented as adjusted hazard ratios (HR) and associated 95% confidence intervals (CI). Multivariable logistic regression models were used to examine the association of receipt of rituximab with sociodemographic and clinical factors through estimation of the odds ratios (OR) and associated 95% CI.Results We obtained data on 642 patients with DLBCL (n=88, 0-19y; n=554, 20-39y). Rituximab use increased from 64% during 2001-2007 to 79% during 2008-2014. The majority of patients who received rituximab were older (20-39y, n=420, 92%, P<0.0001), of NHW race/ethnicity (n=196, 43%, P=0.09), had private insurance (n=311, 68%, P=0.49), resided in higher nSES (4th & 5th quintiles, n=291, 64%, P=0.49), and were treated at a non-NCIDCC (n=309, 68%, P=0.20). Five-year OS improved significantly over time, from 79% (2001-2007) to 87% (2008-2014), and was higher among patients aged 0-19y (91%) vs. those aged 20-39y (82%), as well as for patients who received rituximab (85%) vs. those who did not receive this treatment (77%). In multivariable-adjusted models, the risk of death was about 50% lower among patients who received rituximab compared to those who did not receive it (HR=0.52, 95% CI 0.34-0.79). Patients aged 20-39y had 2.6 times greater risk of death than those aged 0-19y (HR=2.60, 95% CI 1.23-5.50). The hazard of death was significantly higher among Hispanics (HR=1.74, 95% CI 1.09-2.77 vs. NHW), for patients who lacked health insurance (HR=2.21, 95% CI 1.21-4.02 vs. privately insured) or were publicly insured (HR=1.70, 95% CI 1.08-2.66), and for those with advanced stage at diagnosis (HR= 2.81, 95% CI 1.72-4.59 vs. localized). On a multivariable logistic regression analysis in which all variables were mutually adjusted, the odds of receipt of rituximab was significantly higher in the more recent calendar period of diagnosis (2008-2014, OR=3.58, 95% CI 2.17-5.92), among AYAs (vs. 0-19y, OR=9.57, 95% CI 5.33-17.19), among APIs (vs. NHW, OR=1.85, 95% 1.06-3.10), and for patients with advanced stage at diagnosis (vs. localized, OR=1.81, 95% CI 1.06-3.10). Insurance status, treatment facility and nSES were not associated with receipt of rituximab. In our cohort, about 14% of patients had HIV/AIDS. When we excluded these patients from the analysis, the same pattern of associations was observed, although the magnitude of some of the associations was attenuated (Table).Conclusions Our study confirms the benefit of using rituximab on the treatment of children and AYAs with DLBCL. However, the worse survival observed among AYAs and patients of Hispanic race/ethnicity are concerning and warrant further investigation.Although patients who lacked health insurance or were publicly insured had lower survival than private insured patients, insurance status, treatment facility, nSES and Hispanic race/ethnicity were not found to be associated with the receipt of rituximab. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.