Field-testing the MALT-IPI in a single center real-world cohort of patients with extranodal marginal zone lymphoma

The MALT-IPI is widely applied to estimate outcomes in patients with extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT). Although it was developed in the context of the IELSG-19 trial exclusively in patients treated with chlorambucil, rituximab or their combination, it is commonly used across virtually all disease settings. However, its applicability beyond contexts resembling the IELSG-19 trial remains debated, and several studies have proposed modifications to improve prognostic precision in EMZL. Here, we retrospectively analyzed 498 patients with newly diagnosed EMZL at the Medical University of Vienna with the dual objective of evaluating the prognostic performance of the MALT-IPI across clinical subgroups, and to assess whether incorporation of autoimmunity could refine risk stratification. Stratification by the MALT-IPI revealed significantly longer progression-free survival (PFS) and overall survival (OS) in low-risk patients compared with intermediate- and high-risk groups (p<0.001) in unselected patients. However, in subgroup analyses, its discriminatory capacity was restricted to patients with extragastric disease, particularly patients with EMZL of the ocular adnexa or the parotid gland or intestinal EMZL, as well as those receiving systemic therapy. Contrarily, patients with gastric EMZL or those managed with Helicobacter pylori eradication, local therapy or watch-and-wait approaches did not derive consistent prognostic separation. Incorporation of autoimmunity identified a small subgroup with inferior PFS and OS but provided limited incremental prognostic power beyond the established index in most patients. Our results support context-specific applicability of the MALT-IPI and highlight autoimmunity as a prognostically relevant factor in a small cohort of patients.