Data from Cell-of-Origin Subtype Predicts Response to Polatuzumab Vedotin in Large B-cell Lymphoma
Year: 2026
Type: other
Abstract: Purpose: Polatuzumab vedotin (polatuzumab) was approved for up-front treatment of diffuse large B-cell lymphoma in combination with chemoimmunotherapy (Pola-R-CHP) based on the POLARIX trial. However, when stratified by cell of origin (COO), polatuzumab seems to have greater efficacy in activated B-cell than germinal center B-cell (GCB) subtype disease. Most studies of polatuzumab used RNA expression to assess COO, whereas in routine clinical practice, the immunohistochemistry-based Hans algorithm is used. Experimental Design: To assess the impact of COO by immunohistochemistry on polatuzumab efficacy, we conducted a multicenter real-world study of adults with large B-cell lymphoma (LBCL) receiving polatuzumab from 2015 to 2024, split by receipt of polatuzumab in first-line 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 first-line setting and 435 in the relapsed/refractory setting. In the relapsed/refractory cohort, the ORR in non-GCB versus GCB LBCL was 59.7% versus 36.3% [OR, 2.6; 95% confidence interval (CI), 1.77–3.84; P < 0.0001], with a complete response rate of 35.7% versus 17.7% (OR, 2.6; 95% CI, 1.66–4.02; P < 0.0001). Progression-free survival was longer for patients with non-GCB versus GCB COO (HR, 0.64; 95% CI, 0.5–0.83; P = 0.0006). In the first-line cohort, ORR, complete response rate, and progression-free survival were similar in non-GCB versus GCB LBCL, as hypothesized based on outcomes in the Pola-R-CHP arm of POLARIX, suggesting that the addition of polatuzumab overcomes the adverse risk of non-GCB COO in patients receiving R-CHOP. Conclusions: Based on these data, COO classification by the Hans algorithm is a strong predictor of polatuzumab efficacy in LBCL, informing real-world treatment decisions.
Authors: Edward R. Scheffer Cliff, Guido D. Pelaez, Fei Wan, Varun Iyengar, Jihao Zhou, Kevin Chung, Nayef Abdel-Razeq, Jessica Allen, Ajay Major, John Sharp, Narendranath Epperla, Patrick Gould, Hua-Jay J. Cherng, Samin Houshyar, Danielle S. Wallace, Ryan C. Lynch, Avyakta Kallam, Matthew G. Mei, Reid W. Merryman, Michelle Fleyshman, Joanna M. Rhodes, Adam Kidwell, Timothy S. Fenske, Nikita Malakhov, Erin Mulvey, Marcus P. Watkins, Muhamad Alhaj Moustafa, Talal Hilal, Grzegorz S. Nowakowski, Yucai Wang, Pallawi Torka, David A. Russler-Germain
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W7118300762