Ki‐67 Proliferation Patterns Are Predictive of Early Progression and Inferior Outcomes in Grade 1–2 Follicular Lymphoma
Year: 2023
Type: article
Study design: Observational Study
Abstract: Background: Follicular lymphoma (FL) is the most prevalent indolent B-cell non-Hodgkin lymphoma (B-NHL). Progression of disease within 24 months (POD24) and transformation to large B-cell lymphoma (LBCL) are known adverse outcomes in grade 1–2 FL. There is a need to develop practical and sensitive biomarkers to risk-stratify these patients (pts) at diagnosis. Ki-67 staining is a widely available biomarker without a defined role in FL, however has potential to better highlight the tumor microenvironment (TME) based on its known colocalization with subsets of T-cells. We thus set out to characterize high-risk pt features based on Ki-67 immuno-architectural patterns of grade 1–2 FL at diagnosis. Methods: Diagnostic biopsy slides from 68 pts with grade 1–2 FL without concurrent LBCL treated at the University of Chicago were collected from 11/2001 to 2/2021. Grade 1–2 histology was confirmed by H&E-stained slides, and Ki-67 stained slides were scored for immuno-architectural features including peripheral follicular pattern Ki-67% (pKI), central/diffuse follicular pattern Ki-67% (cKI), and extrafollicular Ki-67% (eKi). Outcomes were assessed by overall survival (OS), occurrence of POD24 from time of initial treatment, and transformation to LBCL. Outcomes were compared with log-rank and Mann-Whitney tests of significance. Results: Median age at diagnosis was 61 years (yrs) (IQR 52–69 yrs), and 57% of pts were male. Eleven (16%) pts experienced POD24 from time of first treatment, and 17 (25%) subsequently transformed to LBCL. Median follow-up time was 9.0 yrs (IQR 6.1–11.7 yrs). Median pKi for pts with POD24 was 20% (IQR 11%–40%) versus 3% (IQR 0%–15%) for those without POD24 (p = 0.01). Median cKi for pts with POD24 was 20% (IQR 9%–30%) versus 5% (IQR 2%–15%) for those without POD24 (p = 0.02). Median eKi for pts with POD24 was 5% (IQR 4%–6%) versus 3% (IQR 1%–3%) for those without POD24 (p = 0.04). There was no association between pKi, cKi, or eKi with transformation to LBCL. Pts with pKI ≥ 10% also had significantly inferior 5-yr OS of 85% (95% CI: 73%–99%) compared with 100% for those with pKi < 10% (p < 0.01) (Figure 1A). A cKI score ≥ 10% was not associated with inferior survival outcomes (Figure 1B). Keywords: diagnostic and prognostic biomarkers, indolent non-Hodgkin lymphoma, pathology and classification of lymphomas Conflicts of interests pertinent to the abstract G. Venkataraman Consultant or advisory role EUSA Pharma Honoraria: ASH J. P. Kline Consultant or advisory role Janssen, Sanofi, COTA Healthcare Honoraria: Kite Pharma Inc./Gilead Research funding: Merck, Kite Pharma Inc./Gilead, Seattle Genetics, Verastem Oncology P. A. Riedell Consultant or advisory role Abbvie, Genmab, ADC Therapeutics, Pharmacyclics, Novartis, BMS, Kite/Gilead, Nurix Therapeutics, Nektar Therapeutics, Takeda, Intellia Therapeutics, Sana Biotechnology, BeiGene, Janssen, CVS Caremark Honoraria: Novartis, Kite Pharma Research funding: BMS, Kite/Gilead, Novartis, MorphoSys, CRISPR Therapeutics, Calibr, Xencor, Fate Therapeutics, Tessa Therapeutics M. R. Bishop Consultant or advisory role Celgene, Kite Pharma Inc./Gilead, CRISPR Therapeutics, Takeda, Novartis Honoraria: Kite Pharma Inc./Gilead, BMS, Incyte, Agios, Celgene Other remuneration: Novartis
Source: Hematological Oncology
DOI: 10.1002/hon.3165_534
Authors: A. E. Rojek, G. Venkataraman, L. Fabi, H. Venkatraman Ravisankar, J. P. Kline, P. A. Riedell, M. R. Bishop, A. T. Pearson, S. M. Smith
Institution: University of Chicago
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4379979793