Evaluation of Ki-67 expression and large cell content as prognostic markers in MZL: a multicenter cohort study

Marginal zone lymphoma (MZL) can have varied presentations and pathologic features, including high Ki-67 expression ( > 20%) as well as increased numbers of large B cells (LC). However, there are limited data available demonstrating the prognostic significance of these variables in patients with MZL. In this multi-institutional retrospective cohort study of patients with MZL treated at 10 centers, we evaluated the association between the presence of Ki-67 expression and increased LCs on survival and risk of histologic transformation (HT). A total of 785 patients were included (60% with extranodal MZL, 20% with nodal MZL, and 20% with splenic MZL). Among the 440 patients with Ki-67 staining, 22% had high Ki-67 (Ki-67 >20%). The median progression-free survival (PFS) for patients with high Ki-67 was 5.4 years compared to 7.0 years for patients with low Ki-67 (HR = 1.45, 95%CI = 1.03-2.05). Ki-67 > 20% strongly correlated with high LDH level. The risk of HT was higher in patients with increased Ki-67 than those without (5-year risk, 9.8% vs 3.87%, p = 0.01). Twelve percent of patients had LC reported on biopsy with 6% having >10% LC. The presence of LC was associated with high Ki-67 (p < 0.001), but not associated with shorter PFS or overall survival (OS). The cumulative risk for HT was higher in patients with LC compared to those without LC (5-year risk, 9.4% vs 2.9%, p = 0.04). Receipt of anthracycline-based therapy did not impact PFS or OS in either group. Ki-67 staining >20% was a prognostic factor for worse survival and strongly correlated with elevated LDH. Novel therapies should be investigated for their potential ability to overcome the high-risk features in MZL. Our data reinforce the importance of obtaining biopsies at relapse or progression, particularly in patients with baseline high Ki-67 and increased LCs, given their increased risk for HT.

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Publication Details

Journal
Blood Cancer Journal
Published
2024-10-18
DOI
https://doi.org/10.1038/s41408-024-01162-z
Citations
10
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
4.25

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article

Evaluation of Ki-67 expression and large cell content as prognostic markers in MZL: a multicenter cohort study

Reem Karmali, Marcus P. Watkins, Geoffrey Shouse, Praveen Ramakrishnan Geethakumari et al.
10 citations
Blood Cancer Journal
Lymphoma Diagnosis and Treatment
4.25
article

Evaluation of Ki-67 expression and large cell content as prognostic markers in MZL: a multicenter cohort study

Reem Karmali, Marcus P. Watkins, Geoffrey Shouse, Praveen Ramakrishnan Geethakumari, Stefan Klaus Barta, Kaitlin Annunzio, Montreh Tavakkoli, Timothy S. Oh, Pallawi Torka, Adam J. Olszewski, Andrea Anampa‐Guzmán, Heather Reves, Emily Hansinger, Natalie Sophia Grover, Nancy L. Bartlett, Narendranath Epperla, Colin Thomas, Beth Christian
article en
10 citations

Abstract

Marginal zone lymphoma (MZL) can have varied presentations and pathologic features, including high Ki-67 expression ( > 20%) as well as increased numbers of large B cells (LC). However, there are limited data available demonstrating the prognostic significance of these variables in patients with MZL. In this multi-institutional retrospective cohort study of patients with MZL treated at 10 centers, we evaluated the association between the presence of Ki-67 expression and increased LCs on survival and risk of histologic transformation (HT). A total of 785 patients were included (60% with extranodal MZL, 20% with nodal MZL, and 20% with splenic MZL). Among the 440 patients with Ki-67 staining, 22% had high Ki-67 (Ki-67 >20%). The median progression-free survival (PFS) for patients with high Ki-67 was 5.4 years compared to 7.0 years for patients with low Ki-67 (HR = 1.45, 95%CI = 1.03-2.05). Ki-67 > 20% strongly correlated with high LDH level. The risk of HT was higher in patients with increased Ki-67 than those without (5-year risk, 9.8% vs 3.87%, p = 0.01). Twelve percent of patients had LC reported on biopsy with 6% having >10% LC. The presence of LC was associated with high Ki-67 (p < 0.001), but not associated with shorter PFS or overall survival (OS). The cumulative risk for HT was higher in patients with LC compared to those without LC (5-year risk, 9.4% vs 2.9%, p = 0.04). Receipt of anthracycline-based therapy did not impact PFS or OS in either group. Ki-67 staining >20% was a prognostic factor for worse survival and strongly correlated with elevated LDH. Novel therapies should be investigated for their potential ability to overcome the high-risk features in MZL. Our data reinforce the importance of obtaining biopsies at relapse or progression, particularly in patients with baseline high Ki-67 and increased LCs, given their increased risk for HT.

Blood Cancer JournalVol. 14(1)
Northwestern University (US), University of North Carolina at Chapel Hill (US), Roswell Park Comprehensive Cancer Center (US), City Of Hope National Medical Center (US), Memorial Sloan Kettering Cancer Center (US), Thomas Jefferson University (US), Washington University in St. Louis (US), University of Utah (US), Brown University (US), Huntsman Cancer Institute (US), Southwestern Medical Center (US), UNC Lineberger Comprehensive Cancer Center, The Ohio State University (US), University of Pennsylvania (US), The University of Texas Southwestern Medical Center (US)
Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Gilead Sciences, Celgene, F. Hoffmann-La Roche, Regeneron Pharmaceuticals, Celldex Therapeutics, TG Therapeutics, Adaptive Biotechnologies, BeiGene, Incyte, Seagen, MorphoSys, Ipsen, Genentech, Kite Pharma, Pharmacyclics, Daiichi Sankyo Europe
Openalex Percentile: Top 5%
Lymphoma Diagnosis and Treatment
4.25
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