The Predictive Value of Cell-of-Origin Subtype By Hans Algorithm in 718 Patients with Large B Cell Lymphoma Receiving Polatuzumab Vedotin

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.652-652
• Main Authors: Cliff, Edward R Scheffer, Pelaez, Guido D, Wan, Fei, Iyengar, Varun, Zhou, Jihao, Chung, Kevin, Abdel-Razeq, Nayef, Major, Ajay, Allen, Jessica M, Sharp, John, Epperla, Narendranath, Gould, Patrick, Cherng, Hua-Jay J, Houshyar, Samin, Wallace, Danielle S, Lynch, Ryan C., Kallam, Avyakta, Mei, Matthew, Merryman, Reid W., Fleyshman, Michelle, Rhodes, Joanna M., Kidwell, Adam, Fenske, Timothy S, Mulvey, Erin, Watkins, Marcus P., Alhaj Moustafa, Muhamad, Hilal, Talal, Nowakowski, Grzegorz S., Wang, Yucai, Torka, Pallawi, Russler-Germain, David A
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-202153

Background: Polatuzumab vedotin (Pola) is an antibody drug conjugate targeting CD79b that incorporates the microtubule disrupting monomethyl auristatin E payload. Pola was approved in 2023 for the upfront treatment of diffuse large B cell lymphoma (DLBCL) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (polaRCHP) based on the POLARIX trial. However, the activity of pola appears to vary based on DLBCL cell of origin (COO) subtype, with greater efficacy in activated B cell (ABC) DLBCL compared to germinal center B cell (GCB) DLBCL (Russler-Germain Blood 2023). When outcomes in POLARIX are stratified by COO, polaRCHP demonstrated progression free survival (PFS) and overall survival (OS) benefits over RCHOP in patients with ABC but not GCB subtype DLBCL (PFS HR 0.34 ABC vs 1.03 GCB, OS HR 0.27 ABC vs 1.64 GCB; Morschhauser ASH 2023 and FDA data). Most prospective studies of pola used gene expression to assess COO, which is not readily clinically available. This study aims to examine if COO subtype by Hans algorithm (based on CD10, BCL6, and MUM1 expression by immunohistochemistry) is predictive of pola responses and outcomes in patients with large B cell lymphoma (LBCL). Methods: We conducted a retrospective, multicenter observational study of adults with LBCL who received pola (monotherapy or in combination) from 2015-2024 with Hans algorithm COO data and response assessment available. Patients were stratified by receipt of pola in the frontline vs relapsed/refractory (R/R) setting. The primary endpoint was overall response rate (ORR) to pola-based treatment in GCB vs non-GCB subtypes. Secondary endpoints included complete response rate (CRR), PFS, and OS. For time to event endpoints, patients responding to pola who received CAR T or stem cell transplantation prior to progression were censored at time of cellular therapy. Demographics were summarized by descriptive statistics. Comparative and survival analyses used Chi squared/Fischer exact tests and Kaplan Meier analysis. Data cutoff was July 1, 2024. Results: 718 patients were included. Median follow-up was 15 months (interquartile range [IQR] 8-32). Median age at LBCL diagnosis was 66 years (IQR 56-74); 62% were men; 69 (10%) had double hit lymphoma (DHL); 129 (18%) had underlying low grade lymphoma. Pola was used in the frontline setting in 293 (41%) patients, of whom 139 (47%) had GCB vs 154 (53%) non-GCB COO. Of the 426 patients receiving pola for R/R LBCL (including one pat