Cell-Of-Origin Subtype Predicts Response to Polatuzumab Vedotin in Large B Cell Lymphoma
- Author(s)
- Cliff, ERS; Pelaez, GD; Wan, F; Iyengar, V; Zhou, J; Chung, K; Abdel-Razeq, N; Allen, J; Major, A; Sharp, J; Epperla, N; Gould, P; Cherng, HJ; Houshyar, S; Wallace, DS; Lynch, RC; Kallam, A; Mei, MG; Merryman, RW; Fleyshman, M; Rhodes, JM; Kidwell, A; Fenske, TS; Malakhov, N; Mulvey, E; Watkins, MP; Alhaj Moustafa, M; Hilal, T; Nowakowski, GS; Wang, Y; Torka, P; Russler-Germain, DA;
- Journal Title
- Clinical Cancer Research
- Publication Type
- Online publication before print
- Abstract
- PURPOSE: Polatuzumab vedotin (polatuzumab) was approved for upfront treatment of diffuse large B-cell lymphoma (DLBCL) in combination with chemoimmunotherapy (Pola-R-CHP) based on the POLARIX trial. However, when stratified by cell-of-origin (COO), polatuzumab appears to have greater efficacy in activated B-cell (ABC) than germinal center B-cell (GCB) subtype. Most studies of polatuzumab used RNA expression to assess COO, whereas, in routine clinical practice the immunohistochemistry-based Hans algorithm is used. METHODS: To assess the impact of COO by immunohistochemistry on polatuzumab efficacy, we conducted a multicenter real-world study of adults with LBCL receiving polatuzumab from 2015-2024, split by receipt of polatuzumab in frontline versus relapsed/refractory settings. The primary endpoint was overall response rate (ORR) to polatuzumab-based treatment in GCB versus non-GCB relapsed/refractory LBCL. RESULTS: Of 740 patients, 305 received polatuzumab 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, 95%CI 1.77-3.84, p<0.0001), with complete response rate (CRR) of 35.7% versus 17.7% (OR 2.6, 95%CI 1.66-4.02, p<0.0001). Progression-free survival (PFS) was longer for patients with non-GCB versus GCB COO (HR 0.64, 95%CI 0.5-0.83, p=0.0006). In the frontline cohort, ORR, CRR, and PFS were similar in non-GCB versus GCB LBCL, as hypothesized based on outcomes in the Pola-R-CHP arm of POLARIX, suggesting addition of polatuzumab overcomes the adverse risk of non-GCB COO in patients receiving R-CHOP. CONCLUSIONS: Based on these data, COO classification by Hans algorithm is a strong predictor of polatuzumab efficacy in LBCL, informing real-world treatment decisions.
- Department(s)
- Haematology
- Publisher's Version
- https://doi.org/10.1158/1078-0432.Ccr-25-2392
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-11-20 05:57:42
Last Modified: 2025-11-20 05:57:51