Biomarkers for Risk Stratification in Patients with Previously Untreated Follicular Lymphoma Receiving Anti-CD20-based Biological Therapy

Aliyah R. Sohani, Matthew J. Maurer, Sharmila Giri, Brandelyn Pitcher, Amy Chadburn, Jonathan W. Said, Nancy L. Bartlett, Myron S. Czuczman, Peter Martin, Cara A. Rosenbaum, Sin Ho Jung, John P. Leonard, Bruce D. Cheson, Eric D. Hsi

Research output: Contribution to journalArticlepeer-review


Follicular lymphoma (FL) is an indolent B-cell neoplasm of germinal center origin. Standard treatment regimens consist of anti-CD20 therapy with or without chemotherapy. While high response rates to initial therapy are common, patients ultimately relapse or have progressive disease. Clinical risk factors such as the Follicular Lymphoma International Prognostic Index (FLIPI) have been identified, but there is a need for prognostic and predictive biomarkers. We studied markers of lymphoma cells and tumor microenvironment by immunohistochemistry in tissue samples from patients enrolled in 1 of 4 phase 2 trials of anti-CD20-based biological therapy for previously untreated grades 1 to 2 or 3A FL. Results were correlated with progression-free survival (PFS) and PFS status at 24 months. The 4 trials included 238 patients (51.1% male, median age: 55 y) with stage III, IV, or bulky stage II disease. By FLIPI, 24.6% had low-risk, 56.8% had intermediate-risk, and 18.6% had high-risk disease. The outcome differed significantly for patients treated with lenalidomide and rituximab (CALGB 50803) compared with the other 3 trials (median: PFS not reached vs. 3.0 y, hazard ratio=3.47, 95% confidence interval: 2.11-5.72); therefore, data were stratified by clinical trial (CALGB 50803 vs. all others) and adjusted for FLIPI risk group. Among 154 patients with available tissue, interfollicular BCL6 positivity, interfollicular CD10 positivity, and elevated Ki67 proliferation index ≥30% within neoplastic follicles were each associated with inferior PFS and a high risk of the early event by PFS status at 24 months. We identify promising biomarkers for FL risk stratification that warrant further validation in phase 3 trials.

Original languageEnglish (US)
Pages (from-to)384-393
Number of pages10
JournalAmerican Journal of Surgical Pathology
Issue number3
StatePublished - Mar 2021


  • BCL6
  • CD10
  • Ki67 proliferation index
  • follicular lymphoma
  • prognostic biomarkers

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine


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