Real-world outcomes in T-cell/histiocyte-rich large B-cell lymphoma: Insights from the largest u.S. cohort to date

Abstract

Abstract Background: T cell/histiocyte-rich large B cell lymphoma (THRLBCL) is a rare and aggressive subtype of diffuse large B cell lymphoma (DLBCL) with distinct pathological and clinical features (Blood PMID: 26980727). It is characterized by a sparse population of malignant B cells amid abundant reactive T cells and histiocytes. Compared to conventional DLBCL, THRLBCL more often presents with advanced-stage disease and frequent extranodal involvement, particularly in the bone marrow, liver, and spleen (Leuk Lymphoma PMID: 31287335). Despite its rarity, national-level analyses provide an opportunity to evaluate care patterns and outcomes. While disparities in access and outcomes between Academic Cancer Programs (ACPs) and Community Cancer Programs (CCPs) have been documented in other malignancies, their impact in THRLBCL is unknown. To our knowledge, this analysis represents the largest national cohort of patients with THRLBCL, using the National Cancer Database (NCDB) to examine demographic, socioeconomic, and survival differences between those treated at ACPs versus CCPs. Methods: We conducted a retrospective analysis of patients diagnosed with THRLBCL in the United States between 2004 and 2022 using the NCDB. Demographic, clinical, and survival data were compared between patients treated at ACPs and CCPs. ACPs included academic and research programs, including NCI-designated comprehensive cancer centers. CCPs comprised community, comprehensive community, and integrated network cancer programs. Kaplan-Meier and Cox proportional hazards models were used to compare overall survival (OS), adjusting for age, race/ethnicity, insurance status, comorbidity score (Charlson-Deyo), and distance from treating facility. Results: Of 1,938 patients diagnosed with THRLBCL, 894 (46%) were treated at ACPs and 632 (33%) at CCPs. The remaining 412 patients (21%) with unknown facility type were excluded. Across both settings, the majority were male (65.5% ACP vs. 65.8% CCP). Patients treated at ACPs were significantly younger (median age 62 vs. 64 years, p < 0.001), with a greater proportion under 60 years (45.0% vs. 39.6%). ACPs served a more racially diverse population, treating higher proportions of Black patients (20.8% vs. 14.9%, p < 0.001) and fewer White patients (73.8% vs. 82.1%, p < 0.001), while Hispanic representation was comparable (7.4% vs. 7.3%). Medicaid coverage was more common among patients at ACPs (9.1% vs. 6.2%, p < 0.001), while Medicare coverage was more prevalent in CCPs (46.0% vs. 38.8%, p < 0.001). Rates of uninsured patients were similar (2.9% ACP vs. 3.2% CCP). Socioeconomically, a greater share of CCP patients resided in neighborhoods with lower educational attainment (68.2% vs. 60.4%, p < 0.001). Most patients in both groups lived in metropolitan areas (80.1% ACP vs. 78.0% CCP, p = 0.002), though patients at ACPs traveled farther for care (median distance 12.2 vs. 9.1 miles, p < 0.001). Advanced disease at diagnosis (Stage IV) was more frequently observed in ACPs (56.9% vs. 48.3%, p < 0.001). Radiation therapy was used less frequently at ACPs (8.8% vs. 11.1%, p = 0.089). Time from diagnosis to initiation of systemic therapy was similar (median 30 days ACP vs. 29 days CCP, p = 0.602), and over 90% of patients received systemic therapy in both settings. Despite demographic, socioeconomic, and disease-related differences, overall survival outcomes were similar. Two-, five-, and ten-year OS rates were 79%, 71%, and 58% for ACPs versus 76%, 68%, and 56% for CCPs, respectively (all p > 0.05). On multivariable Cox regression analysis adjusting for age, stage, comorbidity score, insurance, and distance to care, treatment at an ACP versus a CCP was not independently associated with OS (p = 0.318). Conclusions: In this large national cohort—the most comprehensive analysis of THRLBCL to date—ACPs treated a higher proportion of younger, Black, and socioeconomically disadvantaged patients, many of whom presented with more advanced-stage disease and traveled farther for care. Despite these differences, overall survival was excellent and did not differ significantly between ACPs and CCPs. These findings suggest that while ACPs may serve as referral hubs for more complex cases, CCPs can achieve equivalent outcomes when care is standardized. Continued efforts to expand access to expert care and ensure uniform treatment approaches may help maintain these favorable outcomes across all settings.