Survival benefit of chemoradiotherapy in limited-stage mantle cell lymphoma: a National Cancer Database analysis

Limited-stage mantle cell lymphoma (MCL) is rare, and optimal management remains undefined because of limited representation in clinical studies. We conducted a large population-based analysis using the National Cancer Database to evaluate overall survival (OS) in patients with Ann Arbor stage I to II MCL diagnosed between 2004 and 2015. Initial treatment was categorized to chemotherapy alone, radiotherapy (RT) alone, or combined chemotherapy plus RT (Chemo+RT), and outcomes were further stratified by stage and era of diagnosis (2004-2009 vs 2010-2015) to account for advances in systemic therapy, such as the adoption of bendamustine-rituximab for frontline therapy and the availability of Bruton tyrosine kinase inhibitors for relapsed disease. Among 2428 patients included, median OS for the entire cohort was 8.1 years. Chemo+RT was associated with superior OS compared with chemotherapy alone or RT alone (median OS, 11.2 vs 7.4 vs 8.0 years, respectively; P < .001). This survival benefit was observed in both stage I and stage II diseases and in both eras. On multivariable analysis, treatment with chemotherapy alone (hazard ratio [HR], 1.50) or RT alone (HR, 1.33) was independently associated with inferior OS compared with Chemo+RT. In this, to our knowledge, largest real-world analysis of limited-stage MCL to date, combined chemoimmunotherapy and RT was associated with a clinically meaningful survival benefit, including in the modern treatment era. These findings suggest that combined-modality therapy may be preferred for appropriately selected patients with limited-stage MCL.