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

2024· article· en· W4405273291 on OpenAlexaff
Evgenii Shumilov, Rebecca Wurm‐Kuczera, Andrea Kerkhoff, Meng Wang, Thomas Melchardt, Udo Holtick, Ulrike Bacher, Philipp B. Staber, Paolo Mazzeo, Corinna Leng, David Böckle, Alexander Sebastian Hölscher, Joseph Kauer, Vladan Vučinić, Jakob Rudzki, David Nachbaur, Veit Bücklein, Ulf Schnetzke, Isabelle Krämer, Kai Wille, Alexander Hasse, Bastian von Tresckow, Mathias Hänel, Christian Koenecke, Giuliano Filippini Velázquez, Andreas Viardot, Christoph Schmid, Lorenz Thurner, Dominik Wolf, Martin Dreyling, Peter Dreger, Sascha Dietrich, Ulrich Keller, Ulrich Jäger, Richard Greil, Thomas Pabst, Georg Lenz, Bjoern Chapuy

Bibliographic record

VenueBlood Advances · 2024
Typearticle
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsInnovation Cluster (Canada)
FundersCilagBerlin Institute of HealthSwedish Orphan BiovitrumIncyteBeiGeneAgios PharmaceuticalsRegeneron PharmaceuticalsAmgenAriad PharmaceuticalsGilead SciencesSanofiPfizerLes Laboratories Pierre FabreMorphoSysCelgeneAstraZenecaEli Lilly and CompanyBristol-Myers Squibb
KeywordsMedicineInternal medicineBendamustineRefractory (planetary science)Cytokine release syndromeRituximabOncologySalvage therapyGastroenterologyLymphomaSurgeryChemotherapyImmunotherapyCancerChimeric antigen receptorBiology

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.539
Threshold uncertainty score0.459

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.017
GPT teacher head0.342
Teacher spread0.325 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations24
Published2024
Admission routes1
Has abstractyes

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