Survival Outcomes of Rural Patients with Mantle Cell Lymphoma
Authors: Rubnitz Zach , Vardell Victoria A. , Fitzgerald Lindsey , Bock Allison M. , Shah Harsh , Hu Boyu , Stephens Deborah M. , Ermann Daniel A. 
Published: December 2023

Background
Mantle cell lymphoma (MCL) is a rare and aggressive malignancy, representing approximately 6-8% of all non-Hodgkin lymphomas, and is generally associated with poor outcomes. Patients (pts) with MCL often require intensive up-front treatment with consideration for stem cell transplant consolidation. Due to geographic limitations, pts living in rural areas with MCL may not have access to specialized treatment centers experienced in managing this rare disease. There is a paucity of data available evaluating the impact of rurality in MCL, and it is unknown how population density and access to major metropolitan centers and their healthcare systems may impact survival outcomes.
Methods
The National Cancer Database was used to identify MCL pts diagnosed from 2004-2020. Demographic and treatment characteristics were compared by county level measures of rurality and urban influence, categorized into metropolitan (metro), non-metropolitan urban (urban), and non-metropolitan rural (rural) counties. These data are provided from the 2013 Department of Agriculture Economic Research service data Rural-Urban Continuum Codes which uses population, population density, and commuting distance to determine these codes. Pts without rurality data or who were not treated at the reporting facility were excluded. Kaplan Meier and adjusted Cox regression survival analysis were used to compare overall survival by rural-urban codes.
Results
Of the 29,464 pts with MCL identified, 83.4% (N= 24,849) resided in metro counties, 14.6% (N=4,356) resided in urban counties, 1.9% (N=573) resided in rural counties. Non-metro pts were more likely to be male (70.7% male metro vs 73.0% and 72.1% for urban and rural counties, respectively), with similar age at diagnosis across county types (median age of 68 for metro pts and 69 for rural pts). Rural pts had a higher burden of comorbidities, as determined by the Charlson-Deyo comorbidity index (11.3% of rural pts with a score of 2 or greater, compared to 8.7% urban, and 7.9% of metro pts). Pts from metro counties were more likely to have private insurance (38.5% metro vs. 32.4% for urban and 28.6% for rural pts), where non-metro pts were more often uninsured (3.3% of rural, vs 2.4% of metro) or Medicare insured (61.6% rural vs 53.4% of metro pts). Notably, pts were less likely to be managed with active surveillance if they were from a rural county (4.8% vs 6.9% of metro pts), and were more likely to receive systemic disease related therapy at diagnosis (90.6% rural vs 85.2% metro).
With a median follow up of 42 months, pts from metro counties had a median overall survival (OS) of 70.6 months (95% confidence interval (CI) 68.6-72.7), which was significantly longer than those from urban (61.1 months [95% CI 56.4-65.9], p&lt;0.001) and rural counties (59.8 months [95% CI 54.0-65.6], p&lt;0.001). The survival disparity was persistent for metro, urban, rural pts at 1-year (81%, 80%, and 78% respectively, p&lt;0.001), 5-years (54%, 50%, 50% respectively, p&lt;0.001) and 10-years (36%, 30%, 29% respectively, p=0.066). When referenced to pts from metro counties on Cox regression, non-metro counties had a greater risk of all-cause mortality, with hazard ratio (HR) of 1.13 (95% CI 1.08-1.18; p&lt;0.001) for urban and 1.14 (95% CI 1.02-1.28; p=0.024) for rural pts. When adjusted for age and Charlson-Deyo comorbidity score this survival disparity persisted, with a HR of 1.12 (95% CI 1.07-1.17), p&lt;0.001 for urban pts and HR 1.05 (95% CI 0.94-1.18), p=0.408, for rural pts, when referenced to pts from metro counties.
Discussion
We demonstrate a population density-based survival disparity in MCL pts, finding that pts living in more rural counties have worse survival outcomes. Rural pts had a higher comorbidity burden and were more likely to be underinsured. Additionally, they received less active surveillance, which may indicate delays in diagnosis and/or consultation with an oncologist. Given the rapidly evolving treatment landscape of MCL, these data support the need for efforts to improve healthcare access for MCL pts, such as earlier referrals to academic centers with expertise in MCL management, expanded access to telehealth, rural partnerships with academic medical centers, and programs that support patient and family travel.