Ribrag V, et al. Clinical Lymphoma Myeloma and Leukemia, 2021, 21(5), 309-317.e3
Danvatirsen (AZD9150) was investigated in combination therapies to improve outcomes in relapsed/refractory diffuse large B-cell lymphoma (DLBCL), a condition with limited treatment options after multiple relapses. This phase 1b study assessed the safety and efficacy of combining danvatirsen with durvalumab, an anti-PD-L1 antibody, or tremelimumab, an anti-CTLA-4 antibody, aiming to potentiate endogenous antitumor responses.
Thirty-two patients with relapsed/refractory DLBCL received either durvalumab plus danvatirsen or durvalumab plus tremelimumab. Danvatirsen was administered in an intensive initial dosing schedule followed by weekly maintenance, while durvalumab was delivered every four weeks. The primary endpoint, safety, was met, with treatment-related adverse events observed in 65.6% of patients, predominantly mild to moderate and including increased liver enzymes, anemia, and fatigue.
Efficacy results revealed a limited overall objective response rate of 6.3%, with two patients achieving partial responses. Median progression-free survival was 7.4 weeks, and median overall survival was 28 weeks. Despite modest antitumor activity, analysis suggested that patients with STAT3 mutations or overexpression might derive greater benefit, pointing to a potential biomarker-driven approach for future studies.
