Safety and efficacy of glofitamab for relapsed/refractory large B-cell lymphoma in a multinational real-world study

Safety and efficacy of glofitamab for relapsed/refractory large B-cell lymphoma in a multinational real-world study

Abstract: Glofitamab, a bispecific antibody targeting CD20 and CD3, is approved for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) after at least 2 prior treatment lines, but real-world data are scarce. In this retrospective, multicenter, multinational study, we evaluated the outcomes...

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Main Authors: Evgenii Shumilov, Rebecca Wurm-Kuczera, Andrea Kerkhoff, Meng Wang, Thomas Melchardt, Udo Holtick, Ulrike Bacher, Philipp Staber, Paolo Mazzeo, Corinna Leng, David Böckle, Alexander Hölscher, Joseph Kauer, Natalia Rotter, Vladan Vucinic, Jakob Rudzki, David Nachbaur, Veit Bücklein, Ulf Schnetzke, Isabelle Krämer, Kai Wille, Alexander Hasse, Bastian von Tresckow, Mathias Hänel, Christian Koenecke, Giuliano Filippini Velazquez, Andreas Viardot, Christoph Schmid, Lorenz Thurner, Dominik Wolf, Marion Subklewe, Martin Dreyling, Peter Dreger, Sascha Dietrich, Ulrich Keller, Ulrich Jäger, Richard Greil, Thomas Pabst, Georg Lenz, Björn Chapuy
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Blood Advances
Online Access:http://www.sciencedirect.com/science/article/pii/S2473952924007195
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Summary:Abstract: Glofitamab, a bispecific antibody targeting CD20 and CD3, is approved for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) after at least 2 prior treatment lines, but real-world data are scarce. In this retrospective, multicenter, multinational study, we evaluated the outcomes of 70 patients with r/r DLBCL treated with glofitamab as part of the compassionate use patient program in Germany, Austria, and Switzerland. The median number of prior treatment lines was 4, with 71% of patients refractory to their last treatment. Cytokine release syndrome was observed in 40% of patients (grade 3-4 in 2%), immune effector cell–associated neurotoxicity syndrome in 10% (grade 3 in 1%), and infections in 31% (grade 5 in 3%). The overall response rate was 46%, with 27% achieving complete responses (CR) and 19% partial responses. The median progression-free survival (PFS) was 3.6 months, whereas the median overall survival was 5.7 months. Notably, 13 patients (19%) were in CR 6 months after initiating glofitamab and exhibited durable responses. Elevated lactate dehydrogenase is the most robust predictor of inferior outcome. Patients pretreated with bendamustine within 6 months prior to glofitamab initiation exhibited significantly reduced PFS, suggesting that bendamustine may impair T-cell fitness and hence glofitamab efficacy. In summary, glofitamab demonstrates promising efficacy and a manageable safety profile in heavily pretreated patients with r/r DLBCL in a real-world scenario and the optimal sequence of treatments should use T-cell–depleting agents before glofitamab with caution.
ISSN:2473-9529

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