The Impact of Social Determinants of Health on Peripheral T Cell Lymphoma Outcomes: Treatment Center-Type Emerges as a Powerful Prognostic Indicator

Abstract

Background: Prognostic models in peripheral T cell lymphoma (PTCL) have identified biological factors including age, performance status, LDH, and bone marrow involvement as prognostic for survival. The association of nonbiological factors, termed social determinants of health (SDH), on PTCL outcomes remains unexplored. 

Methods: To evaluate the impact of actionable SDH on PTCL mortality across race groups, we conducted a retrospective cohort study that included all White, Hispanic, Asian/Pacific Islander (PI) and Black adult patients with PTCL (AITL, ALCL, NKTCL and PTCL, NOS), diagnosed from 2000 to 2020, in California. We utilized Chi2 and Wilcoxon rank-sum tests for descriptive metrics and Kaplan-Meier statistics for mortality estimation. Regression models included patient- (age, sex, race, stage, Charlson Comorbidity Index, histology, treatment type, treatment at an academic center, payer), and neighborhood-level factors (socioeconomic (SES) quintile, proportion without a high school diploma, and rural/urban). Risk factors significant in univariate regression at a P-value < 0·10 were incorporated into the multivariable model. 

Findings: Our analysis included 6,158 patients: 51·8% White, 25·8% Hispanic, 14·7% Asians/PI, and 7·6% Black. Hispanics exhibited the longest median survival (33 months) followed by Whites, Blacks, and Asian/PI (25, 20, and 14 months, respectively; P = 0·011). Risk factors independently associated with inferior lymphoma-specific survival (LSS) included Asian/PI compared with NH White race (HR, 1·23; 95% CI, 1·10-1·34; P = 0·0002), AITL and ALCL compared with PTCL, NOS histology (AITL HR, 1·14; 95% CI, 1·02-1·25; P = 0·011 ; ALCL HR, 1·15; 95% CI 1·04-1·26; P = 0·004), academic compared to non-academic facility-type (HR 0·71; 95% CI, 0·64-0·77; P < 0·01), Medicare compared with uninsured status (HR 1·48, 95% CI 1·25-1·73; P < 0·01), and  the lowest three education quartiles compared to the highest education quartile (Q2 HR 1·13; 95% CI 1·01-1·25; P = 0·021; Q3 HR 1·14; 95% CI 1·02- 1·26; P = 0·018; Q4 HR 1·22; 95% CI 1·08-1·36; P < 0·001). In the least resourced patients, histology, treatment, treatment facility-type, payer and education were independently prognostic for LSS. Treatment at an academic institution was associated with a striking improvement in LSS (academic institution: yes= 101 months, no = 17 months; P < 0·01) 

Interpretation: These data identify treatment facility-type, payer and education, as an independent actionable SDH for PTCL mortality.Treatment center-type had the strongest prognostic association with LSS in our PTCL cohort, conferring a risk reduction of PTCL mortality by nearly 30%. Interventions targeted at improving access to academic centers may improve outcomes for all PTCL patients.

Funding: This work was supported by the Jonsson Comprehensive Cancer Center Strategic Plan-aligned program, University of California, Los Angeles.

Declaration of Interest: MM, BM, AS and SC report no competing interests. SL reports research funding to UCLA (clinical trials): Allogene, ImmPACT Bio, Janssen, Pfizer, Regeneron, Bioline, BMS, Kite, and Sanofi. JT reports support from Genetech, Pharmacyclics, Abbvie, ADC Therapeutics, Pfiezer, Regeneron, Genmab. JZ reports Consultant: AstraZeneca, Kiowa Kirin, Seattle Genetics , Myeloid, Astex, CRSPR, Dreon, Acrotech; Grant/Research support: Astra Zeneca, Daichi Sankyo, Dreon , Affimed. Seattle Genetics, Secura Bio; Speaker Bureau- Kiowa Kirin.

Ethical Approval: This study was approved by the UCLA Institutional Review Board and the Committee for the Protection of Human Subjects, California.

Keywords: Peripheral T-cell lymphoma, Social determinants of health