Shifting Demographics and Survival Trends in Mantle Cell Lymphoma Over Two Decades: Age Remains an Independent Predictor of Outcomes
Mantle cell lymphoma (MCL) predominantly affects older adults, and age strongly influences treatment eligibility and outcomes. Although survival has improved with therapeutic advances over the past two decades, evolving patient demographics and disease characteristics may affect these trends. Hence, we aim to characterize temporal changes in demographic and clinical profiles of MCL and evaluate age-stratified survival to determine whether age remains the dominant prognostic factor in the modern era.
Materials and Methods/Case Presentation/Objective:
MCL (ICD-O-3 9673/3, malignant behavior) cases diagnosed between 2000-2023 were selected from SEER 21 database. Inclusion: known age at diagnosis, first primary or first of multiple primaries, and survival ≥1 month. Exclusions: autopsy/death-certificate-only cases. Patients were grouped into three prespecified eras reflecting major changes in MCL therapies: chemoimmunotherapy (2000-2012), BTK inhibitor (2013-2019), and cellular/immunotherapy (2020-2023). Because case-level data lack population denominators, age-adjusted incidence rates were obtained from a SEER*Stat rate session, while case-mix trends were assessed using ordinary least squares regression. Overall survival and cancer-specific survival (CSS) were estimated by Kaplan-Meier analysis across age groups (< 50, 50-59, 60-69, 70-79, and ≥80 years). Multivariable Cox proportional-hazards models evaluated independent predictors of mortality after adjusting for sex, race/ethnicity (non-Hispanic [NH] Black, Hispanic, NH White, Asian Pacific Islander, American Indian and Alaska Native), disease stage (localized, regional, distant, unknown), time period, residence (metropolitan vs. non-metropolitan), marital status (married, single, divorced, widowed, separated), and area-level median income.
Results/Description/Main Outcome Measure(s):
Among 19,736 patients, MCL case counts increased over the study period (+22 cases/year, p< 0.001), with a modest increase in median age at diagnosis (+0.08 years/year, p=0.003), and a growing proportion of Hispanic patients (14.9% to 22.0%, p< 0.001). Stage ascertainment improved over time, as unknown stage declined from 31.5% to 4.0% while distant-stage disease increased (+3.0%/year, p< 0.001).
Survival improved over time across therapeutic eras, with 2-year CSS increasing from 75.5% (2000-2012) to 80.3% (2013-2019) to 82.0% (2020-2023). Despite these temporal improvements, survival has declined steeply with advancing age. Five-year OS declined from ~80% in patients < 50 years to 23% in those ≥80; when dichotomized at age 65, 5-year CSS decreased from 74% in those < 65 to 55% in those ≥65 years-old.
Age remained a strong independent predictor of mortality, with each 10-year increase associated with a 59% higher risk of cancer-specific mortality [HR 1.59, 95% CI 1.56-1.63]. Advanced stage (HR 2.01, 95% CI 1.81-2.24), unmarried status (HR 1.18), and non-metropolitan residence (HR 1.16) were also associated with worse outcomes; female sex was protective (HR 0.78, 95% CI 0.74-0.82).
Conclusion(s).:
Demographics of MCL have evolved with rising case counts and increasing proportion of Hispanic patients. Despite improved survival over the past two decades, age remained a strong independent predictor of cancer-specific mortality, and older age was associated with markedly poorer outcomes. Advanced stage, unmarried status, and non-metropolitan residence were also associated with worse outcomes, while female sex was associated with improved survival. However, improved stage ascertainment may partially reflect stage migration and other case-mix shifts, contributing partly to the observed survival improvements. Limitations of SEER data precluded definitive inference regarding incidence trends and treatment effectiveness.
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