Limited-stage Mantle Cell Lymphoma: Real-world outcomes according to nodal vs. extranodal presentation

Abstract Introduction Mantle cell lymphoma (MCL) treatment has evolved significantly in recent years, with a paradigm shift from traditional chemotherapy-based regimens to targeted therapies and chemo-free combinations. Despite these advances, optimal management strategies for limited-stage (Ann Arbor stage I or II) MCL remain undefined due to limited data. We previously reported outcomes in early-stage MCL, primarily from the pre-rituximab era (Bernard et al., 2013). The present study aims to evaluate clinical characteristics and describe treatment patterns and outcomes in the modern therapeutic context. Methods We conducted a retrospective review of adult patients (≥18 years) diagnosed with stage I–II MCL between January 1, 2003, and October 1, 2024, Princess Margaret Cancer Centre. Patients were identified through the institutional Cancer Registry. Disease presentation was categorized as nodal or extranodal (with or without regional nodal involvement). Treatment modalities were grouped into radiotherapy (RT) alone or chemotherapy-based regimens, which could include RT and/or autologous stem cell transplantation (ASCT). The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses included descriptive statistics, the Kaplan-Meier method, and Cox proportional hazards modeling. Results During the study period, 421 patients were newly diagnosed with MCL, of whom 36 (8.6%) had limited-stage disease (15 stage I, 21 stage II). Eight were staged with PET and the remainder with CT. The median age was 64 years (range 39-91), and 64% were aged ≥60. Treatment regimens included RT alone (28%), chemotherapy plus RT (44%), chemotherapy followed by ASCT (17%), and chemotherapy alone (11%). RT was applied at a median of 30 Gy. Seventeen patients had nodal disease, and 19 had primary extranodal involvement, all located in the head and neck region—oral cavity (63%), nasopharynx (26%), and orbit (11%). With a median follow-up of 72.5 months (range, 4.0–257.0), 13 patients experienced disease progression—10 in the nodal group and 3 in the extranodal group. Progression was significantly more frequent in patients with nodal disease compared to those with extranodal involvement (77% vs. 30%, P=0.007), and among those treated with RT alone compared to chemotherapy or combined modality treatment (54% vs. 13%, P=0.018). Baseline characteristics, including disease stage, age, International Prognostic Index, ECOG performance status, Ki-67 proliferation index, and MCL International Prognostic Index, did not differ significantly between patients with and without progression. OS was also not significantly different between these groups (P=0.236). When analyzed by disease presentation, OS was comparable between the nodal and extranodal groups (228 vs. 165 months; P = 0.78). However, patients with extranodal disease had significantly prolonged progression-free survival (PFS) compared to those with nodal involvement (not reached vs. 72 months; P = 0.023). Baseline characteristics, including age, sex, IPI, ECOG status, and treatment modality, were similar between the two groups, with the exception of a higher prevalence of stage II disease in the nodal group (76% vs. 42%; P = 0.037). In the extranodal group, treatment modality did not significantly affect OS or PFS. In contrast, among those with nodal disease, RT alone was associated with a markedly increased risk of progression compared to chemotherapy-containing regimens (hazard ratio 8.6, 95% CI: 1.7–43.3; P = 0.009). Notably, disease stage did not independently affect PFS or OS in either the nodal or extranodal groups. Conclusion In this cohort, long-term survival outcomes were generally favorable. Extranodal involvement, particularly in the head and neck region, was common and associated with a lower risk of progression and significantly prolonged PFS compared to nodal disease. While treatment modality did not influence outcomes in patients with extranodal disease, chemotherapy-containing regimens demonstrated superior disease control over RT alone in those with nodal presentations.