Intensity of Survivin Expression Correlates with Clinical and Biological Markers of Aggressive R/R DLBCL

Introduction: The SPiReL phase II clinical trial evaluated combination immunotherapy with an immunogenic vaccine formulation to the tumor antigen survivin comprised of maveropepimut-S (MVP-S), pembrolizumab and cyclophosphamide in survivin-expressing relapsed or refractory (R/R) diffuse large B cell...

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Published in:Blood 2023-11, Vol.142 (Supplement 1), p.6124-6124
Main Authors: Usta, Sila, Misura, Alexandra, Roos, Kim, Rashedi, Iran, Amitai, Irina, Jiang, Yidi, Mangoff, Kathryn, Klein, Gail, Forward, Nicholas Allen, Stewart, Douglas A., Mangel, Joy, Tomlinson, George A., Tsui, Hubert, Berinstein, Neil
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Language:English
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Summary:Introduction: The SPiReL phase II clinical trial evaluated combination immunotherapy with an immunogenic vaccine formulation to the tumor antigen survivin comprised of maveropepimut-S (MVP-S), pembrolizumab and cyclophosphamide in survivin-expressing relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL). The efficacy of this survivin-directed T cell educating therapy may be influenced by the survivin antigen burden in the DLBCL. To further explore this potential relationship, we evaluated the heterogeneity of tumor survivin expression in the SPiReL study cohort and its associations with established clinical-pathological DLBLC variables. Methods: Survivin immunohistochemistry (IHC) was performed at NeoGenomics Laboratories (Aliso Viejo, California, USA) on formalin fixed paraffin embedded (FFPE) tumor slides from diagnostic biopsies obtained at trial screening. Inclusion criteria stipulated >10% of tumor cells expressing survivin by IHC. Semi-quantitative survivin expression metrics, as determined by pathologist assessment, included: total percentage of survivin-positive cells; intensity of survivin staining scored as 0 = None, 1+ = Weak, 2+ = Moderate, 3+ = Strong; and H-score, a linear weighted average (% positive cells x staining intensity level). Radiologic tumor burden was measured at up to 4 time points during the trial by computed tomography (CT). Other pathology (e.g. cell of origin) and laboratory biomarkers (e.g. lactate dehydrogenase, LDH) were extracted from clinical results. Results: The mean and median percentage of survivin-positive tumor cells for all enrolled participants (n= 25) was 91% and 99%, respectively. At the per participant level, the range of survivin expression was 50-100% of the cellular content. The heterogeneity of survivin expression intensity among participants is shown in Figure 1. All participants had some proportion of biopsied cells expressing strong (3+) intensity survivin (range: 5-100% of cells, mean: 30% while only 52% of tumors contained non-survivin expressing (0) cells, ranging from 0% to 50% (mean: 9%) Greater proportions of cells that expressed moderate (2+) and/or strong (3+) survivin significantly correlated with clinical and biological markers of aggressive DLBCL. Non-GCB tumours (11/25) showed greater H-scores compared to GCB tumours (212 vs 167, p = 0.0287). Non-GCB tumours contained greater proportions of strong intensity (3+) survivin cells compared to GCB tumours (44% vs 25%, p= 0.045). In a
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2023-189200