Real-World Outcomes in Grade 3B Follicular Lymphoma and Composite Follicular Lymphoma with Diffuse Large B-Cell Lymphoma: A Single-Center, Retrospective Cohort Study in China
Authors: Lv Yufei , Zhang Xiang , Zhu Yanan , Wei Juying , Zhang Xuewu , Ye Xingnong , Tong Hongyan , Jin Jie , Yu Wenjuan 
Published: December 2024

Background: Follicular lymphoma of WHO grade 3B (G3BFL, renamed follicular large B-cell lymphoma in WHO-HAEM5) and Composite Follicular Lymphoma with Diffuse Large B-cell lymphoma (FL/DLBCL), are recognized for their aggressive clinical features. Current treatment guidelines often recommend rituximab-based chemotherapy regimens that include anthracyclines, mirroring the approach for DLBCL. However, a comprehensive understanding of the real-world clinical features and outcomes for patients with G3BFL and composite FL/DLBCL remains scarce.

Aims: To report the clinical features and outcomes of patients with G3BFL and composite FL/DLBCL in real-world settings at our center.

Methods: In this retrospective cohort study, we included patients diagnosed with G3BFL and composite FL/DLBCL at our center from May 2012 to December 2022. Eligible patients had received at least three months of treatment and were administered R(Rituximab)-or O(Obinutuzumab)-CHOP-like chemotherapy regimens. The outcomes included progression-free survival (PFS) and overall survival (OS).

Results: We retrospectively analyzed data from 103 patients, comprising 59 with G3BFL and 44 with composite FL/DLBCL. The cohort included 64 males with a median age of 59 years (range: 30-86), and the majority (50.4%) were under 60 years of age. At the time of diagnosis, 72.8% (75/103) of patients presented with Ann Arbor stage II/IV disease, 38.8% (40/103) had extranodal involvement, and 19.4% (20/103) had bone marrow involvement. Elevated serum lactate dehydrogenase was observed in 41.7% (43/103) of cases, and 13.6% (14/103) had large tumor masses (&gt;6 cm). According to the FLIPI-1 assessment, 27.2% (28/103)as low risk, 13.6% (14/103) as intermediate risk, and 59.2% (61/103) as high risk, while according to FLIPI-2 assessment, 45.6% (47/103) as low risk, 26.2% (27/103) as intermediate risk, and 28.2% (29/103) as high risk.

During a median follow-up period of 36 months (range: 3-147), 37 patients experienced disease relapse, and 14 deaths were recorded, with 8 due to disease progression, 5 due to severe infection, and 1 due to pancreatic cancer. Within the first 24 months post-initial chemotherapy, 17 patients (16.5%) had relapsed or showed disease progression. 52 patients (50.5%) received maintenance therapy after remission, and maintenance therapy included rituximab, lenalidomide or Bruton's tyrosine kinase(BTK) inhibitor.

The median progression-free survival (PFS) and overall survival (OS) for the entire cohort were not reached at the time of analysis. The 3-year OS rate was 84.8% (95% CI: 75.5-90.8), and the PFS rate was 66.3% (95% CI: 55.4-75.1). Composite FL/DLBCL patients exhibited a significantly poorer PFS compared to G3BFL patients, with rates of 72.4% versus 43.2% (HR: 0.5007, 95% CI: 0.2532-0.9900, p=0.0412). However, the OS rate was comparable between the two groups, with 85.1% for G3BFL and 84.7% for FL/DLBCL (HR: 1.069, 95% CI: 0.3689-3.099, p=0.9011).

Summary/Conclusion: Our study revealed that G3BFL patients treated with R-or O-CHOP-like chemotherapy had superior progression-free survival compared to those with composite FL/DLBCL, despite similar baseline characteristics. Future research will focus on updating outcomes with larger cohorts and extended follow-up to further inform clinical practice.