Clinical-Demographic Profile, Prognostic Factors and Outcomes in Classic Follicular Lymphoma Stratified by Staging and Tumor Burden: Real-World Evidence from a Large Latin American Cohort

Abstract

Background: Clinical staging (CS) and tumor burden (TB) play a significant role in FL prognosis and direct its up-front therapy. The aim of this study is to report prognostic factors and clinical outcomes in newly-diagnosed FL patients stratified according to CS and TB in early-stage (ES) disease, advanced-stage with low tumor burden (AS-LTB) and advanced-stage with high tumor burden (AS-HTB). Methods: Two hundred fourteen patients with FL grades 1-3A had baseline clinical characteristics and outcomes assessed. Survival according to up-front immunochemotherapeutic (ICT) regimens was assessed in the AS-HTB subgroup. Independent predictors for OS, PFS, POD-24, and Histological Transformation (HT) were identified. Results: Seventy-five percent of cases were categorized as AS-HTB, 13.5% as AS-LTB and 11.5% as ES. With a median follow-up of 8.15 years, the estimated 5-year OS and PFS were 75.4% and 57.2%, respectively. OS, but not PFS was markedly decreased in AS-HTB FL patients compared to ES and AS-LTB cases. POD-24 rate was 21.7% and overall mortality rate was 38.7% during the entire follow-up. The annual cumulative rate of HT to high-grade B-cell lymphoma (HGBCL) was 0.5%, and higher in AS-HTB cases, in comparison to ES and AS-LTB. Considering patients with AS-HTB there were no differences in clinical outcomes among cases submitted to ICT based on R-CHOP, R-CVP and regimens containing purine analogs. Additionally, ECOG ≥ 2, hypoalbuminemia, B-symptoms and HT were independently associated with poor survival. High content of centro-blasts (grade 3A), involvement of ≥3 nodal sites by FL and rituximab omission in up-front therapy predicted POD-24. Conclusions: FL has marked clinical-prognostic heterogeneity, translated into diverse CS and TB subcategories. Here, we demonstrated that FL patients classified as AS-HTB demonstrated decreased survival and higher rates of HT to HGBCL compared to ES and AS-LTB cases. Prognostic factors identified in our analysis may help to identify FL patients with higher-risk of HT and early-progression (POD-24).

Keywords: clinical outcomes; follicular lymphoma (FL); histological transformation (HT) to high-grade B-cell lymphoma (HGBCL); prognostic factors; progression of disease within 24 months from initial therapy (POD-24); staging; treatment modalities; tumor burden.

Figure 1

Study design.

Figure 2

OS (A) and PFS (B) in the whole cohort of FL patients grade 1–3A (N = 214). The survival curves were constructed using the Kaplan–Meier method.

Figure 3

OS (A) and PFS (B) curves according to subgroup stratified by clinical staging and tumor burden (N = 214). Blue-line: ES; Red-line: AS-LTB; Green-line: AS-HTB. The survival curves were constructed using the Kaplan–Meier method. The comparison among curves used the Log-Rank test.

Figure 4

OS curves (A) and PFS (B) for AS-HTB FL patients according to up-front therapy (N = 156). Dark-blue line: R-CHOP; Red-line: R-CVP; Green-line: ICT-P; Light-blue line: palliative regimens. The survival curves were constructed using the Kaplan–Meier method. The comparison among curves used the Log-Rank test.

Figure 5

Annual cumulative rate for HT to HGBCL in the whole cohort (A) and cumulative rate for HT to HGCBL according to clinical staging and tumor burden (B). Blue-line: ES; Red-line: AS-LTB; Green-line: AS-HTB, p = 0.06. The comparison of cumulative incidence for HT to HGBCL among different categories was calculated using the Log-Rank test.

Figure 6

Prognostic factors for OS (A), PFS (B) and HT to HGBCL (C) identified in univariate analysis. Univariate analysis used the Cox regression method and the results were presented as forest plots.