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

TitleBiomarkers for Risk Stratification in Patients With Previously Untreated Follicular Lymphoma Receiving Anti-CD20-based Biological Therapy.
Publication TypeJournal Article
Year of Publication2021
AuthorsSohani AR, Maurer MJ, Giri S, Pitcher B, Chadburn A, Said JW, Bartlett NL, Czuczman MS, Martin P, Rosenbaum CA, Jung S-H, Leonard JP, Cheson BD, Hsi ED
JournalAm J Surg Pathol
Volume45
Issue3
Pagination384-393
Date Published2021 03 01
ISSN1532-0979
KeywordsAdult, Aged, Aged, 80 and over, Antigens, CD20, Antineoplastic Agents, Immunological, Biomarkers, Tumor, Clinical Trials as Topic, Disease Progression, Female, Humans, Immunohistochemistry, Ki-67 Antigen, Lymphoma, Follicular, Male, Middle Aged, Neoplasm Staging, Neprilysin, Prospective Studies, Proto-Oncogene Proteins c-bcl-6, Recurrence, Risk Assessment, Risk Factors, Rituximab, Time Factors, Treatment Outcome, Tumor Microenvironment, United States, Young Adult
Abstract

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.

DOI10.1097/PAS.0000000000001609
Alternate JournalAm J Surg Pathol
PubMed ID33136585
PubMed Central IDPMC7878306
Grant ListUG1 CA233329 / CA / NCI NIH HHS / United States
U10 CA180821 / CA / NCI NIH HHS / United States
UG1 CA233180 / CA / NCI NIH HHS / United States
UG1 CA233191 / CA / NCI NIH HHS / United States
U10 CA180882 / CA / NCI NIH HHS / United States
U24 CA196171 / CA / NCI NIH HHS / United States
UG1 CA233339 / CA / NCI NIH HHS / United States
Related Faculty: 
Amy Chadburn, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700