Metabolic tumor volume is an independent predictor of worse survival in 57 elderly patients with DLBCL

Abstract

Abstract INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is no longer considered a unique entity. In addition to molecular features, metabolic biomarkers, such as metabolic tumor volume (MTV), emerged as significant prognostic factors and have been integrated into prognostic scores (e.g. IMPI). However, information on prognostication in the elderly population is scant. The aim of this study is to evaluate the role of metabolic parameters at baseline and throughout first-line therapy in elderly DLBCL patients. METHODS: We retrospectively collected data from consecutive patients over 65 years of age with a diagnosis of DLBCL, actively treated between October 2012 to March 2024 at the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan. Eligible patients should had PET scan at baseline, after 4 cycles of front-line therapy (interim PET, iPET) and at the end of treatment (EoT). PET scans were reviewed by two independent nuclear radiologists. RESULTS: Fifty-seven patients were included in the study. At diagnosis, median age was 75 years (range, 64-87) with 30% over 80 years of age. Twenty-seven (47%) pts were male, 41 (72%) with advanced stage (79% with extranodal involvement) and 37 (65%) having increased LDH. Overall, 38 (67%) pts had IPI 3-5, and 34 (59%) had intermediate-high/high aaIPI. 52 subjects had DLBCL-NOS, 3 HGBCL and 4 transformed indolent lymphomas. According to the Hans algorithm, 25 (44%) pts had GCB and 25 (44%) had a non-GCB phenotype. 50 (88%) patients received standard chemoimmunotherapy (CHT) (i.e. RCHOP/RCOMP), 4 (7%) reduced-intensity CHT (e.g. R-miniCHOP/COMP) and 3 (5%) intensified CHT. Radiotherapy was delivered in 6 (11%) pts as consolidation. At iPET, 36 (63%) pts obtained complete metabolic response (CMR) (29 with Deauville Score 1, 4 with DS2, 3 with DS3), 7 (13%) had partial response (DS4). Fourteen (25%) pts had progressive disease (DS5), one switched to second-line therapy and the others completed the scheduled therapy because of tumor burden decrease. At EoT PET, 46 (81%) pts achieved CMR, 6 (10%) PMR, while 5 (9%) pts progressed. All patients with DS4 at iPET converted to CMR at EoT. Among those with DS5 at iPET, 36% converted to PMR and 43% to CMR, while 3 pts (21%) experienced progressive disease. With a median follow-up of 42 months (5-95), 14 (24%) pts had disease progression. Median progression-free survival (PFS) was not reached (range, 3.6 – NR), median OS was 86 months (range, 5-94). The estimated 2-year PFS and OS was 82% (69-90%) and 83% (70-91%), respectively. In univariate analysis, age over 80 years (p=0.004), higher aaIPI (p=0.04) and reduced-intensity CHT were significantly associated with worse PFS and OS. Baseline MTV higher than 817,91 mL and increasing DS at iPET impacted negatively on PFS (p<0.007 and p=0.001, respectively) and OS (p=0.001 and p=0.003, respectively). In multivariate analysis, higher MTV at baseline remained an independent prognostic factor for survival (p=0.015). Among pts with CMR at iPET, those with baseline MTV > 817,910 mL had significantly worse PFS and OS (p=0.0001). CONCLUSIONS: In elderly DLBCL patients, baseline MTV is a strong independent prognostic factor for survival, even among those achieving complete metabolic response at interim PET. Integrating MTV into PET-based response assessment may enhance risk stratification by identifying high-risk patients who might benefit from tailored therapeutic approaches.