Usta Sila, Misura Alexandra, Rashedi Iran, Amitai Irina, Roos Kim, Jiang Yidi, Mangoff Kathryn, Klein Gail, Forward Nicholas, Stewart Douglas, Mangel Joy, Tomlinson George, Tsui Hubert, Berinstein Neil L
Sunnybrook Research Institute, Toronto, Canada.
Department of Immunology, University of Toronto, Toronto, Canada.
Leuk Lymphoma. 2025 Jan;66(1):84-94. doi: 10.1080/10428194.2024.2403668. Epub 2024 Sep 27.
SPiReL is a phase II clinical trial evaluating combination immunotherapy, pembrolizumab and cyclophosphamide, with maveropepimut-S, in survivin-expressing relapsed/refractory (R/R) Diffuse Large B Cell Lymphoma (DLBCL). We describe baseline tumor survivin expression and associations with clinico-pathological variables in 25 participants. The median number of survivin-expressing cells was 99%, and the intensity of survivin expression within tumors was heterogeneous by semi-quantitative immunohistochemistry assessment. Tumors with higher numbers of cells expressing 2+/3+ survivin were associated with characteristics of poor outcome, (Lactate dehydrogenase and cell-of-origin). Greater total baseline tumor area was associated with lower proportions of 1+ cells and greater proportions of 2+/3+ cells. High intensity survivin expression is associated with aggressive clinical features supporting a pathobiological role in R/R DLBCL. Future prognostic models incorporating survivin as a clinical biomarker require assessment of intensity, overall expression and should include potential threshold effects of survivin in DLBCL pathobiology.