Revised MALT-IPI: A new predictive model that identifies high-risk patients with extranodal marginal zone lymphoma

Abstract

Extranodal marginal zone lymphoma (EMZL) is a heterogeneous disease with a subset of patients exhibiting a more aggressive course. We previously reported that EMZL with multiple mucosal sites (MMS) at diagnosis is characterized by shorter survival. To better recognize patients with different patterns of progression-free survival (PFS) we developed and validated a new prognostic index primarily based on patient's disease characteristics. We derived the "Revised mucosa-associated lymphoid tissue International Prognostic Index" (Revised MALT-IPI) in a large data set (n = 397) by identifying candidate variables that showed highest prognostic association with PFS. The revised MALT-IPI was validated in two independent cohorts, from the University of Iowa/Mayo Clinic (n = 297) and from IELSG-19 study (n = 400). A stepwise Cox regression analysis yielded a model including four independent predictors of shorter PFS. Revised MALT-IPI has scores ranging from 0 to 5, calculated as a sum of one point for each of the following- age >60 years, elevated LDH, and stage III-IV; and two points for MMS. In the training cohort, the Revised MALT-IPI defined four risk groups: low risk (score 0, reference group), low-medium risk (score 1, HR = 1.85, p = .008), medium-high risk (score 2, HR = 3.84, p < .0001), and high risk (score 3+, HR = 8.48, p < .0001). Performance of the Revised MALT-IPI was similar in external validation cohorts. Revised MALT-IPI is a new index centered on disease characteristics that provides robust risk-stratification identifying a group of patients characterized by earlier progression of disease. Revised MALT-IPI can allow a more disease-adjusted management of patients with EMZL in clinical trials and practice.

Figure 1.. Progression-free survival (PFS) and overall survival (OS), positive predictive value (PPV) for PFS and time-dependent area under the curve for PFS in University of Miami training set.

Kaplan-Meier curves of PFS by Revised MALT-IPI (A) and MALT-IPI (B) scores. Kaplan-Meier curves of OS by Revised MALT-IPI (C) and MALT-IPI (D) scores. PPV as function of time for PFS (E). Time-dependent area under the curve (AUC) for PFS (F). Time-dependent PPV was evaluated in the high-risk group (score 3+ for Revised MALT-IPI, and 2+ for MALT-IPI) using the Kaplan-Meier estimator. Color bands are 95% confidence limits.

Figure 2.. Event-free survival (EFS) and overall survival (OS) in the MER validation set.

Kaplan-Meier curves of EFS for Revised MALT-IPI (A) and MALT-IPI (B) scores in MER validation set. Kaplan-Meier curves for OS for Revised MALT-IPI (C) and MALT-IPI (D) scores.

Figure 3.. Progression-free survival (PFS) and overall survival (OS) in the IELSG-19 validation set.

Kaplan-Meier curves of PFS for Revised MALT-IPI (A) and MALT-IPI (B) scores. Kaplan-Meier curves of overall survival (OS) for Revised MALT-IPI (C) and MALT-IPI (D) scores.