An Analysis of Cell-of-Origin in Diffuse Large B-Cell Lymphoma in Systemic Lupus Erythematosus, Including Molecular and Clinical Factors Associated with Survival

Basile Tessier-Cloutier¹, David Twa², Eva Baecklund³, Randy Gascoyne⁴, Nathalie A. Johnson⁵, Carin Backlin³, Diane L. Kamen⁶, Ann E. Clarke⁷, Rosalind Ramsey-Goldman⁸, Jennifer LF Lee⁹, Pedro Farinha⁴ and Sasha Bernatsky¹⁰, ¹Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada, ²Department of Medicine, University of British Columbia, Vancouver, BC, Canada, ³Department of Medical Sciences, Uppsala University, Uppsala, Sweden, ⁴Department of Pathology, British Columbia Cancer Agency, Vancouver, BC, Canada, ⁵Department of Oncology, McGill University, Montreal, QC, Canada, ⁶Medicine/Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC, ⁷Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada, ⁸FSM, Northwestern University, Chicago, IL, ⁹Medicine, Research Institute of the McGill University Health Centre, Montreal, QC, Canada, ¹⁰Divisions of Rheumatology and Clinical Epidemiology, The Research Institute of the McGill University Health Centre, Montreal, QC, Canada

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Cancer, Malignancy and systemic lupus erythematosus (SLE)

Session Information

Date: Sunday, October 21, 2018

Title: Systemic Lupus Erythematosus – Clinical Poster I: Clinical Manifestations and Comorbidity

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Systemic lupus erythematosus (SLE) is associated with increased risk of diffuse large B-cell lymphoma (DLBCL). DLBCL is routinely classified by cell-of-origin (COO), with non-germinal centre B-cell (GCB) indicating poorer prognosis in the general population. We studied COO subtyping in SLE patients diagnosed with DLBCL, and overall survival.

Methods: We evaluated 20 cases of SLE with DLBCL. In tissue microarrays, immunohistochemistry analysis was performed (BCL2, MYC, BCL6, CD10, CD20, FOXP1, GCET1, MUM1). We examined associations between molecular and clinical features, including overall survival (time to death, all-cause).

Results: Of the 20 DLBCL SLE cases (Table 1), 12/20 cases (60%) were classified as non-germinal centre B-cell (GCB) whereas 8/20(40%) were classified as GCB using Hans or Choi algorithms. MYC and BCL2 protein expression was positive in 6/20 (30%) and 8/20(40%) SLE cases, respectively with 2/20 (10%) co-expressing both markers.

The median survival for all 20 cases was 39 (mean 64) months. As expected, non-GCB cases had worse survival. In both univariate and multivariable Cox proportional hazards models, both non-GBC type and nodal status (any nodal involvement versus none) were associated with lower survival (Table 2). Stratification of cases by nodal status revealed that SLE duration at DLBCL diagnosis was much longer in cases presenting with nodal-only involvement and that BCL2 expression tended to be greater in patients presenting with extra-nodal involvement only. We were unable to detect any molecular or clinical features differing by COO subtype. SLE patients presenting exclusively with extranodal DLBCL were associated with better survival despite higher BCL2 protein expression (which normally indicates poor prognosis).

Conclusion: We present novel data characterizing DLBCL in SLE. Sixty percent of the DLBCL in SLE patients were non-GCB. The nodal and extranodal distribution was similar between patient with SLE and the general population, but extranodal disease occurred more often with short SLE duration and was associated with longer over-all survival. Since non-GCB DLBCL rely on the activation of the NF-κB and JAK-STAT pathways, future assessments of the links between SLE and DLBCL could focus on genetic factors related to the TNF superfamily (TNFSF4), TNF-α, TNF Alpha Induced Protein 3, and other related pathways.

Table 1. Descriptive features of the SLE-DLBCL (n=20) subjects

Variable	Median [IQR]
Sex (female)	2/20 (90)
Age at SLE Diagnosis	45 [36-54]
Age at time of DLBCL diagnosis	58 [48-66]
SLE duration at DLBCL diagnosis	11 [5-18]
Variable	N (%)
Diagnosed after 1991	12 (60)
Nodal-only involvement	10 (50)
Only extranodal involvement	7 (35)
MYC positive	6 (30)
BCL2 positive	8 (40)
BCL6 positive	7 (35)
Dual positive, MYC and BCL-2	2 (10)
Non-germinal B-cell origin (Hans)	12 (60)

Table 2. Cox proportional hazards ratio (HR) for survival in SLE-DLBCL (n=20).

Variable (reference)	Unadjusted HR (95%CI)	*Adjusted HR (95%CI)**
Sex (female)	2.64 (0.95-7.37)	4.49 (1.06-19.0)
Year of DLBCL diagnosis (years)	0.97 (0.92-1.02)	0.94 (0.88-1.01)
Any nodal-involvement	0.29 (0.10-0.98)	0.09 (0.03-0.26)
Non-germinal B-cell origin cell type(Hans)	0.28 (0.08-0.93)	0.08 (0.02-0.43)

*The adjusted model included all four variables in this table.

Disclosure: B. Tessier-Cloutier, None; D. Twa, None; E. Baecklund, None; R. Gascoyne, None; N. A. Johnson, None; C. Backlin, None; D. L. Kamen, None; A. E. Clarke, Bristol-Myers Squibb, 5,AstraZeneca, 5,Exagen Diagnostics, 5,AstraZeneca, 9,Celgene Corporation, 9; R. Ramsey-Goldman, Exagen Diagnostics, Inc, 2; J. L. Lee, None; P. Farinha, None; S. Bernatsky, None.

To cite this abstract in AMA style:

Tessier-Cloutier B, Twa D, Baecklund E, Gascoyne R, Johnson NA, Backlin C, Kamen DL, Clarke AE, Ramsey-Goldman R, Lee JL, Farinha P, Bernatsky S. An Analysis of Cell-of-Origin in Diffuse Large B-Cell Lymphoma in Systemic Lupus Erythematosus, Including Molecular and Clinical Factors Associated with Survival [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/an-analysis-of-cell-of-origin-in-diffuse-large-b-cell-lymphoma-in-systemic-lupus-erythematosus-including-molecular-and-clinical-factors-associated-with-survival/. Accessed .

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