High Ki67 Index Is Associated with Shorter Progression Free Survival in Follicular Lymphoma Patients Treated with Frontline Immunochemotherapy

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.4385-4385
• Main Authors: Han, Jianmin, McCall, Chad M, Isom, Scott, Smith, Wesley, Jenneman, Dakota, Begley, Stephanie, Bose, Rupali, Seegars, Mary Beth, Hsi, Eric D., Ghosh, Nilanjan
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-180106

Introduction The Follicular Lymphoma International Prognostic Index (FLIPI) is a commonly used prognostic tool in follicular lymphoma (FL). However, there is a need for better risk stratification to predict risk of progression after frontline chemoimmunotherapy. Ki67 proliferation index has prognostic value in many lymphomas and is widely available in clinical laboratories. However, the impact of Ki67 on outcomes in FL have not been conclusive. Studies have been limited by the method of quantifying Ki67 (entire specimen or intrafollicular [IF]), heterogeneous treatments, or small single institution studies. Moreover, the impact of Ki67 on predicting disease progression at 24 months (POD24) is unknown. We sought to study the predictive value of Ki67 on PFS in FL treated with Bendamustine Rituximab (BR) or RCHOP with or without Rituximab maintenance (RM) as first line therapy at 2 tertiary care centers. Methods This study was conducted with approval by the Wake Forest University Health Sciences IRB. We retrospectively analyzed 122 patients with FL (grade 1-3A) from 2010 to 2021 at Atrium Health (AH) Levine Cancer Institute (n=72) and AH Wake Forest Baptist Medical Center (n=50) who underwent first line therapy with BR or RCHOP and had tissue/slides available for analysis. Clinical data was collected through electronic medical record review. Archival slides and paraffin-embedded blocks were retrieved. Ki67 immunohistochemistry (IHC) (SP6, Cell Marque, Rocklin, CA), was performed if it was not available from the original work-up (8 cases). CD21 IHC (1F8, Dako, Denmark) was performed in select cases to confirm the presence of follicles in order to assess IF Ki67. Diagnosis, grade, and Ki67 stains were evaluated by 2 hematopathologists. The IF Ki67 index was determined by visual estimate to the nearest 10%. All cases with scores between 20-40% were re-reviewed to achieve a consensus score. Ki67 controls were exchanged between the two centers to ensure equivalent staining. Comparisons of patient characteristics were done by Kruskal-Wallis test for continuous variables (age) or Chi-square tests (categorical variables). Survival analysis was performed using Kaplan-Meier estimation and log-rank testing. Cox proportional hazards modeling was used for multivariable progression free survival (PFS) analysis. Results The clinical and pathologic characteristics are shown in Table 1. No differences in demographics [age, stage, cytologic grade, FLIPI, IF Ki67 status (