Brooks Taylor R, Zabor Emily C, Bedelu Yohanna, Yang Xi, Karimi Yasmin H, Nedved Adrienne N, Wang Yucai, Dave Nikita K, Landsburg Daniel J, Baron Kelsey, Hu Boyu, Trotier Daniel, Pophali Priyanka A, Miller Jordan, Grover Natalie S, Reinert Catherine, Major Ajay, Schwarz Tenley, Patel Krish, Salafian Kiarash, Ayers Emily C, Sundaram Suchitra, Brody Joshua D, McKenna Marshall, Tiger Yun Kyoung Ryu, Sears-Smith Megan, Ghosh Nilanjan, Peterson Chelsea, Khan Cyrus, Bliven Sean P, Narkhede Mayur, Gibson Alyssa, Kline Justin, Munoz Javier, Garza Morales Rodolfo, Ho Carrie, Smith Stephen D, Niu Alex, Hernandez-Ilizaliturri Francisco J, Chinyengetere Fadzai, Dave Sandeep S, Abdel-Razeq Nayef, Alhaj Moustafa Muhamad, Caimi Paolo, Hill Brian T
Cleveland Clinic, Cleveland, Ohio, United States.
Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, United States.
Blood. 2025 Jul 15. doi: 10.1182/blood.2025029117.
Epcoritamab and glofitamab are CD20-directed bispecific antibodies approved in the US for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Limited data exist for patients treated outside of trials. Patients with R/R DLBCL receiving commercial epcoritamab or glofitamab between January 1, 2023 and October 15, 2024 were collected from 21 US institutions. Among 245 patients, 156 received epcoritamab and 89 received glofitamab, 113 were refractory to front-line therapy, 40 had MYC and BCL2 and/or BCL6 rearrangements, 147 received prior chimeric antigen receptor T-cell therapy, and 174 patients would have been ineligible for registrational trials. The overall response rate (ORR) for epcoritamab and glofitamab was 51% (23% complete response, [CR]) and 53% (30% CR), respectively. Median progression-free survival (mPFS) was 2.6 months (95% confidence interval [CI] 2.0 to 3.8 months), and median overall survival (mOS) was 7.8 months (95% CI 6.2 to 11.0 months). The 6-month PFS was 36% (95% CI 30% to 44%) and the 6-month OS was 60% (95% CI 54% to 67%). Both trial ineligibility and undetectable CD20 pre-bispecific portended shorter PFS and OS. Of 17 individuals with paired biopsies, 15 (88.2%) lost CD20 expression after bispecifics with a median time to progression of 3.7 months. This analysis including R/R DLBCL patients shows the ORR to CD3/CD20 BsAbs was comparable to pivotal trials, although PFS and OS were lower. Baseline undetectable levels of CD20 was associated with poor outcomes. These results demonstrate the activity of BsAbs in R/R DLBCL and underscore the importance of target antigen expression.
埃普可妥单抗和格洛妥单抗是在美国获批用于复发或难治性（R/R）弥漫性大B细胞淋巴瘤（DLBCL）的CD20导向双特异性抗体。关于在试验之外接受治疗的患者的数据有限。从美国21家机构收集了在2023年1月1日至2024年10月15日期间接受商业性埃普可妥单抗或格洛妥单抗治疗的R/R DLBCL患者。在245例患者中，156例接受了埃普可妥单抗治疗，89例接受了格洛妥单抗治疗，113例对一线治疗难治，40例有MYC和BCL2及/或BCL6重排，147例接受过嵌合抗原受体T细胞治疗，174例患者不符合注册试验的条件。埃普可妥单抗和格洛妥单抗的总体缓解率（ORR）分别为51%（完全缓解率[CR]为23%）和53%（CR为30%）。中位无进展生存期（mPFS）为2.6个月（95%置信区间[CI]为2.0至3.8个月），中位总生存期（mOS）为7.8个月（95%CI为6.2至11.0个月）。6个月无进展生存率为36%（95%CI为30%至44%），6个月总生存率为60%（95%CI为54%至67%）。试验不符合条件和双特异性治疗前CD20检测不到均预示着较短的无进展生存期和总生存期。在17例有配对活检的个体中，15例（88.2%）在接受双特异性抗体治疗后失去了CD20表达，中位疾病进展时间为3.7个月。这项纳入R/R DLBCL患者的分析表明，CD3/CD20双特异性抗体的ORR与关键试验相当，尽管无进展生存期和总生存期较低。基线CD20检测不到与不良预后相关。这些结果证明了双特异性抗体在R/R DLBCL中的活性，并强调了靶抗原表达的重要性。
