Does low-grade follicular lymphoma with high proliferation index require a different treatment strategy? A single center experience.
Authors: Vusqa Urwat Til , Arner Brooke , Jiwani Rahim , Gagianas Georgia , Khan Cyrus , Lister John , Samhouri Yazan 
Published: June 2023

e19537 Background: Follicular lymphoma is the most common indolent non-Hodgkin lymphoma (NHL). It accounts for 35% of all NHL. FL is divided into three grades based on the proportion of centroblasts. The clinical aggressiveness increases from grade 1 to 3a, but this does not translate to a different therapeutic approach. Some FL patients have a high proliferation index despite having low grade. We assume patients with high proliferation index FL have a more aggressive disease requiring a different therapeutic approach. Here, we examine this theory in a cohort of 145 patients with follicular lymphoma. Methods: This is a retrospective study of patients diagnosed with FL between 01/01/2011 to 12/31/2021. Patients with histological grade 1-3a and reported proliferation index were included. Low grade is defined as grades 1 and 2. A high grade is defined as grade 3a. A high proliferation index (PI) is defined as Ki67 ≥ 30%. Patients were divided into three groups: low grade/high PI (LG/HP), low grade/low PI (LG/LPI), and high grade (HG). Variables collected included age, gender, race, Ann Arbor staging, PET SUV max, FLIPI score, and treatment details. The primary endpoint is progression-free survival. Secondary endpoints include overall survival (OS) and time to first treatment. Univariate and multivariate Cox regression models were used to analyze predictors of PFS. Survival estimates were calculated using the Kaplan-Meier method and compared using the Log-rank test. Results: We identified 145 patients with follicular lymphoma. The median age was 64. The majority were males (54.5%), whites (94.5%) and had Ann Arbor stage of 3 (42.8%). The median SUV max was 10.6. More than half of the patients were in the LG/LP (60%) compared with LG/HP (22.1%) and HG (17.9%). The median follow-up was 48.7 months. Male gender (HR 1.88, CI 1.04-3.4, p 0.03), Ann Arbor stage 3 (HR 4.3, CI 1.0-18.5, p 0.48) and 4 (HR 8.1, CI 1.9-34.8, p 0.005), PET SUVmax (HR 1.06, CI 1.9-1.1, p 0.001), and grade 3 disease (HR 2.2, CI 1.1-4.2, p 0.02) were associated with increased risk of progression. However, on multivariate analysis, only stage 4 (HR 13.1, 95% CI 1.7-104.0, p 0.02) was associated with an increased risk of progression. Adjusted 4-year PFS was 76% for LG/LP, 71% for LG/HG, and 49% for HG. There was no difference in median OS or time to treatment initiation. Conclusions: Our analysis showed that the median PFS for LG/HP patients is numerically worse than LG/LP, but it did not reach statistical significance. In contrast to previous reports, the trajectory of LG/HG is closer to LG/LP group rather than the HG group. Although outcomes are slightly worse for LG/HP compared with LG/LG, it does not justify a different treatment approach. However, a closer follow-up is warranted. Our study is limited by its retrospective nature and its inherent bias; using cox regression model to adjust for baseline characteristics would help mitigate this bias.