Clinical Outcomes of Low Histologic Grade Follicular Lymphoma with High Proliferation Index

Background: Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphoma (NHL) accounting for ~35% of NHL and often have a clinically indolent course. PET/CT max SUV ≥10 and high proliferative index are associated with FL at high risk for transformation to aggressive lymphoma (Schöder, 2005; Rossi, 2020). A subset of patients (pts) with low histologic grade and high proliferation index (LG-HPI) have a more aggressive clinical course with inferior overall survival (OS) compared to low grade, low proliferation index (LG-LPI) FL patients (Wang, 2005). The aim of our study was to identify outcomes for patients with LG-HPI FL at our institution. Methods: We conducted a single center, retrospective study of FL diagnosed from 1/1/2015-1/1/2021. Demographic information, diagnoses, laboratory results, medications, pathology, and radiology reports were collected from pts' electronic medical records. Pathology specimens were de-identified and retrospectively reviewed by two pathologists. Review included comprehensive evaluation of histologic grade, proliferation index by Ki-67 percentage (Ki-67%), immunohistochemical staining, and c-MYC immunohistochemical staining. Biopsies were classified as LG-LPI if Grade 1-2 and Ki-67 was Results: 152 pts were diagnosed with FL and included for analysis. Patient characteristics are summarized in Table 1. Median age at diagnosis for all pts was 65.9 years. Sixty-three pts had LG-LPI, 61 LG-HPI, and 28 HG pts. Ten pts transformed to DLBCL (2 LG-LPI, 5 LG-HPI, 3 HG). Treatment regimens included initial observation (n = 44), anti-CD20 therapy alone (n = 24), chemo-immunotherapy (n = 53), and other (n = 31). Median TTFT was 1.27 mo (range 0-115.2 mo). There was moderate correlation between SUV of biopsied lesion ≥10 and Ki-67 percentage (ROC Area 0.6175). Median PFS was longer for LG-LPI compared to LG-HPI (78.6 vs 57.8 mo, p = 0.04, HR 2.37) but not between LG-HPI and HG (57.8 vs 61.3 mo respectively, p = 0.32) (Figure 1A). Median OS was not reached in any cohort with median follow up of 29.5 mo. There was no difference in OS between LG-LPI vs LG-HPI (p = 0.53) (Figure 1B). Histologic grade, proliferation index, Ann Arbor Staging, FLIPI score, PET/CT SUV intensity (max or of biopsied lesion), presence of c-Myc staining, or initial treatment regimen were not associated with median PFS or OS in either subgroup on univariate analysis. Conclusions: In our cohort, PFS was shorter for LG-HPI compared to LG-LPI but with a similar trajectory to that of HG FL, consistent with prior reports. No differences were seen in OS between LG-HPI and LG-LPI, and no covariates of interest including histologic grade, proliferation index, Ann Arbor Staging, FLIPI score, PET/CT SUV intensity, presence of c-Myc staining, or initial treatment regimen were associated with differences in PFS or OS. Our study is limited by a short follow up time compared to prior published cohorts (29.5 vs 98.4 mo). PET/CT SUV values of ≥10 have moderate predictive value for higher proliferative disease and can aid in identifying patients with higher proliferative disease. Longer follow up is needed to determine if LG-HPI impacts OS. References: 1. SchöderH, et al. Intensity of 18fluorodeoxyglucose uptake in positron emission tomography distinguishes between indolent and aggressive non-Hodgkin's lymphoma. J Clin Oncol 2005;23:4643-51. 2. Rossi C, et al. Baseline SUVmaxis related to tumor cell proliferation and patient outcome in follicular lymphoma. Haematologica 2020;Online ahead of print. 3. Wang SA, et al. Low histologic grade follicular lymphoma with high proliferation index: morphologic and clinical features. Am J Surg Pathol2005;29:1490-6. Figure 1 Figure 1. Disclosures Allen: Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Other: Equity Ownership; Bristol Myers Squibb: Other: Equity Ownership; Alexon: Research Funding. Rhodes: Conquer Cancer Foundation Young Investigator Award: Other: Grant/Research Support; AbbVie, Genentech, Pharmacyclics, TG Therapeutics: Other: Consultant.