Simplified Molecular International Prognostic Index as an eligibility criterion for clinical trials: Analysis of the Turkish Lymphoma Study Group's large B-cell lymphoma cohort

Abstract

Comparative first-line trials in large B-cell lymphoma (LBCL) have mostly failed over the last decade. Failures were commonly attributed to overestimation of the progression risk for the control arms, bringing the precision of the international prognostic index (IPI) into scrutiny. Simplified molecular IPI (smIPI), introduced at American Society of Hematology 2023, was developed to address the shortcomings of IPI. This study investigated smIPI and its potential implications as trial eligibility criteria among a multicentre LBCL cohort of 1439 patients. Patients diagnosed between 2012 and 2024 were included. Data were collected from institutional archives. The primary end-point was risk stratification for progression-free survival (PFS). Kaplan-Meier and Cox regression methods were used for survival analyses. The smIPI reclassified 38.2% and 5.3% of patients to higher and lower risk groups from IPI, respectively. Patients reclassified to higher risk groups by smIPI had an increased risk of progression than the rest of the group (hazard ratio = 1.34, p = 0.003). High-risk groups classified by IPI and smIPI had similar outcomes (3-year PFS 54.9% vs. 56.3%); however, the high-risk group size was expanded by 35.2% when defined by smIPI. The smIPI is easily applicable and more sensitive than IPI in identifying patients under high risk of progression who are ideal candidates to participate in clinical research.