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

ABSTRACT: The mucosal-associated lymphoid tissue (MALT)-International Prognostic Index (IPI) is widely applied to estimate outcomes in patients with extranodal marginal zone lymphoma (EMZL) of 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 patients who were low-risk compared with intermediate- and high-risk groups (P< .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. On the contrary, 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.