Cell-of-origin subtype predicts response to polatuzumab vedotin in large B –cell lymphoma: multinational real-world study

Polatuzumab vedotin (polatuzumab) was approved for upfront treatment of diffuse large B-cell lymphoma (DLBCL) in combination with chemoimmunotherapy (Pola-R-CHP), However, when stratified by cell-of-origin (CCO), polatuzumab appears to have greater efficacy in activated B-cell subtype (ABC) than in germinal center B-cell (GCB) subtype. A multinational real-world study in adults with LBCL receiving polatuzumab from 2015-2024 investigated the impact of CCO on polatuzumab efficacy. The primary endpoint was overall response rate (ORR) to polatzumab-based treatment in GCB versus non-GCBB relapsed/refractory LBCL. Of 740 patient, 305 received treatment in the frontline and 435 in the relapsed/refractory setting. In the relapsed/refractory cohort, ORR in non-GCB versus GCB LBCL was 59.7% versus 36.3% (OR 2.6; p<0.0001) with complete response in 35.7% versus 17.7% (OR 2.6; p<0.0001). Progression-free survival was longer in the non-GCB versus GCB COO (HR 0.64; p=0.0006). In the frontline cohort, ORR, CRR, and PFS were similar in non-GCB versus GCB LBCL. The authors conclude that COO classification is a strong predictor of polatuzumab efficacy in LBCL.