Racial and socioeconomic disparities in clinical trial participation and outcomes in systemic peripheral T-cell lymphoma (PTCL): A multicenter retrospective Study

Abstract

Abstract Background: Peripheral T-cell Lymphoma (PTCL) is an aggressive and heterogenous disease with known survival disparities across racial and ethnic groups (Adams et al. 2016). The causes remain incompletely understood but may include differences in socioeconomic status (SES), access to care, clinical trial participation, and disease biology. In this retrospective study, the primary aim is to investigate disparities in trial participation and outcomes by race and SES in systemic PTCL, and examine how clinical trial enrollment may mitigate these differences. Methods: We conducted a multicenter retrospective study of adults diagnosed with systemic PTCL between 2010-2022 across 10 academic centers in the U.S. SES was measured using 2019 zip code–linked census data to assign income quintiles and Social Deprivation Index (SDI); High SDI (above the US median) indicates greater socioeconomic disadvantage. Overall survival (OS) was defined from diagnosis to death or last follow-up. Survival difference was tested by log-rank and Cox proportional hazards analysis. All multivariable models included age, sex, race/ethnicity, stage, ECOG, Charlson Comorbidity Index (CCI), treatment center, first line (1L) complete remission (CR), histology, and trial enrollment. Trial enrollment differences were tested by logistic regression. Trial eligibility was approximated using ECHELON-2 criteria. Results: Among 621 patients, median age was 62 (IQR 51-71); 52% were non-Hispanic White (NHW), 25% non-Hispanic Black (NHB), 18% Hispanic, and 5% Asian. Subtypes included PTCL-NOS (35%), AITL (31%), ALCL (18%; 12% ALK−, 6% ALK+), and ATLL (15%), with ATLL found exclusively in NHB (46%) and Hispanic (21%) patients. Most (78%) had stage III/IV disease; 43% had IPI ≥3, and 44% had CCI ≥3. With a median follow up of 66 months (m), the median OS for this cohort was 68m; 121m among those enrolled on a 1L trial vs. 61m among those not enrolled (p=.03). By univariable analysis, NHB, age, stage, ECOG, CCI ≥ 3, ATLL, and high SDI were associated with lower OS while higher number of 1L treatment cycles, 1L CR, and trial enrollment were associated with higher OS. In multivariable analysis, increased age, stage, ECOG, and ATLL remained associated with worse OS, while 1L CR (HR 0.40, p<.001) and trial enrollment (HR 0.66, p=.04) remained associated with better OS. After excluding ATLL, 1L CR and trial enrollment continued to predict better OS in multivariable analysis. Significant disparities were observed across race/ethnicity and SES: Trial participation 1L was lower in NHB compared to NHW patients (7.1% vs. 16%; p=.02), and by multivariable analysis, NHB patients were less likely to enroll on a trial (OR 0.32, p=.01). After excluding ATLL, NHB patients continued to be less likely to enroll on a trial (OR 0.29, p=.01). Trial eligibility differed by race/ethnicity as only 35% of NHB patients and 43% of Hispanic patients met baseline lab and performance status criteria, compared to 63% of NHW patients (p<.001). Trial eligibility differences by race were driven by ECOG (p=.004), absolute neutrophil count (p<.001), and creatinine (p=.02). These differences remained significant (p<.05) when excluding patients with ATLL. NHB patients were less likely to receive novel agents compared to NHW patients (19% vs. 33%; p<.01) and had lower CR rates than NHW patients (39% vs. 62%, p=.001). NHB and Hispanic patients were more likely to reside in lower income quintiles (p<.001) and high SDI areas (p<.001). Patients with higher SDI had significantly worse OS (p=.002); among these patients, trial enrollment trended toward improved OS (HR 0.62, p=.08). Conclusion: In this large multicenter cohort with systemic PTCL, racial and SES disparities were evident with significantly lower trial participation in NHB patients and differences in clinical trial eligibility by race/ethnicity. These disparities persisted even when excluding ATLL, an aggressive subtype of PTCL that was found exclusively in NHB and Hispanic patients. Importantly, however, trial enrollment was consistently associated with longer survival and appeared to mitigate differences in survival for patients from high SDI neighborhoods. Future efforts should prioritize expanding equitable trial access, refining eligibility criteria, and delineating system-level barriers to trial participation.