Intensity of survivin expression linked to features of aggressive relapsed/refractory diffuse large B-cell lymphoma

• Published in: Leukemia & lymphoma 2025-01, Vol.66 (1), p.84-94
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - metabolism; Drug Resistance, Neoplasm; Female; Humans; Immunohistochemistry; Inhibitor of Apoptosis Proteins - genetics; Inhibitor of Apoptosis Proteins - metabolism; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphoma, Large B-Cell, Diffuse - mortality; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Middle Aged; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Prognosis; Recurrence; Survivin - genetics; Survivin - metabolism; Treatment Outcome
• ISSN: 1042-8194; 1029-2403; 1029-2403
• DOI: 10.1080/10428194.2024.2403668

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.