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

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.

Authors

Institutions

Publication Details

Journal
Blood Advances
Published
2024-12-11
DOI
https://doi.org/10.1182/bloodadvances.2024014903
Citations
20
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
5.65

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Kai Wille, Richard Greil, Christian Koenecke, David Böckle et al.
20 citations
Blood Advances
CAR-T cell therapy research
5.65
article

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

Kai Wille, Richard Greil, Christian Koenecke, David Böckle, Udo Holtick, Philipp Bernhard Staber, Ulrich Bernd Keller, Giuliano Filippini Velázquez, Ulrich Jäger, Georg Lenz, Paolo Mazzeo, Bastian von Tresckow, Vladan Vučinić, Ulf Schnetzke, Veit Bücklein, Thomas Pabst, Alexander Hasse, Martin H. Dreyling, Rebecca Wurm‐Kuczera, Alexander Sebastian Hölscher, Joseph Kauer, Christoph Schmid, David Nachbaur, Sascha Dietrich, Isabelle Krämer, Mathias Hänel, Andreas Viardot, Lorenz Thurner, Ulrike Bacher, Bjoern Chapuy, Dominik Wolf, Thomas Melchardt, Nicole Rotter, Andrea Kerkhoff, Peter Dreger, Jakob Rudzki, Evgenii Shumilov, Meng Wang, Corinna Leng
article en
20 citations

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.

Blood AdvancesVol. 9(15)
Augsburg University (US), Innsbruck Medical University (AT), Universität Innsbruck (AT), Heidelberg University (DE), Paracelsus Medical University (AT), University Hospital of Bern (CH), University Hospital Augsburg (DE), University Hospital Heidelberg (DE), LMU Klinikum (DE), Medizinische Hochschule Hannover (DE), Humboldt-Universität zu Berlin (DE), Düsseldorf University Hospital (DE), MSB Medical School Berlin (DE), Tyrolean Cancer Research Institute (AT), German Cancer Society (DE), University Hospital Münster (DE), DC Cancer Consortium (US), Universitätsmedizin Göttingen (DE), Essen University Hospital (DE), Cancer Research Institute of the Slovak Academy of Sciences (SK), Innovation Cluster (Canada) (CA), University Hospital Leipzig (DE), Krankenhaus der Elisabethinen (AT), Jena University Hospital (DE), University Hospital Cologne (DE), University Hospital Ulm (DE), Austrian Breast & Colorectal Cancer Study Group (AT), West German Heart and Vascular Center Essen (DE), Klinikum Chemnitz (DE), Johannes Wesling Klinikum Minden (DE), Hannover Re (Germany) (DE), Heinrich Heine University Düsseldorf (DE), University of Duisburg-Essen (DE), University of Göttingen (DE), Medical University of Vienna (AT), Charité - Universitätsmedizin Berlin (DE), Ludwig-Maximilians-Universität München (DE), Saarland University (DE)
Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, Gilead Sciences, Ariad Pharmaceuticals, Celgene, Regeneron Pharmaceuticals, Les Laboratories Pierre Fabre, Agios Pharmaceuticals, BeiGene, Incyte, Swedish Orphan Biovitrum, MorphoSys, Berlin Institute of Health, Cilag
Openalex Percentile: Top 3%
CAR-T cell therapy research
5.65
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.