Loncastuximab tesirine in heavily pretreated patients with large B-cell lymphoma: a German Lymphoma Alliance analysis

For patients with large B-cell lymphoma progressing after multiple lines of therapy few treatment options remain, including the new CD19-directed antibody-drug conjugate loncastuximab tesirine (lonca). To further elucidate its efficacy and safety, we conducted a real-world analysis including data from 31 German centers. Ninety-three heavily pre-treated patients received lonca in third and later line of therapy. 76% had received treatment with chimeric antigen receptor T-cells (n=55), bispecific antibodies (BsAbs) (n=56) or both (n=40). The overall response rate was 27% and complete response rate was 10%. Median progression-free (mPFS) and overall survival (mOS) were 2.2 and 4.4 months, respectively. Median PFS of responders was 11.4 months. Toxicity was acceptable, with grade ≥ 3 infections (13%) being the most common adverse event. Patients receiving subsequent allogeneic stem cell transplantation survived significantly better than the remaining non-consolidated patients (mOS: 15.2 vs. 3.8 months, p=0.048). In multivariable analysis, no response to the last therapy prior to lonca (OS - HR: 2.5, p=0.014) and secondary IPI (PFS/OS - HR: ≥2.0, p≤0.024) were significantly associated with poor outcomes. Lonca demonstrated a favorable safety profile with moderate efficacy in heavily pretreated patients. While enabling timely access to subsequent therapy, efficacy in earlier lines with combination partners may further increase response rates and durability of response.

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Journal
Blood Advances
Published
2026-09-18
DOI
https://doi.org/10.1182/bloodadvances.2026020742
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
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article

Loncastuximab tesirine in heavily pretreated patients with large B-cell lymphoma: a German Lymphoma Alliance analysis

Norbert Schmitz, Igor Age Kos, Kai Wille, Maika Klaiber-Hakimi et al.
Blood Advances
Lymphoma Diagnosis and Treatment
article

Loncastuximab tesirine in heavily pretreated patients with large B-cell lymphoma: a German Lymphoma Alliance analysis

Norbert Schmitz, Igor Age Kos, Kai Wille, Maika Klaiber-Hakimi, Niklas Gebauer, Dimitrios Mougiakakos, Enver Aydilek, Gerald Wulf, Stefan Wirths, Giuliano Filippini Velázquez, Christoph Kimmich, Marcel Teichert, Fabian Müller, Paolo Mazzeo, Bastian von Tresckow, Vladan Vučinić, Philipp Berning, Ulf Schnetzke, Martin Dreyling, Susanne Ghandili, Alexander Sebastian Hölscher, Joseph Kauer, Vanja Zeremski, Micha Peeck, Thomas Weber, Sascha Dietrich, Isabelle Krämer, Mathias Hänel, Philipp Gödel, Andreas Viardot, Leo Hansmann, Lorenz Thurner, Philipp Faustmann, Bjoern Chapuy, Christian Schultze‐Florey, Andrea Kerkhoff, Evgenii Shumilov, Lina Kolloch, Tobias Tix, Anna Ossami Saidy, Meng Wang, Bertram Glass, Florian H. Heidel, Mathias Lutz, Philipp Nakov, Maximilian Seib, Christiane Pott, Christoph Brey, Stephan de Bra, Friedrich-Linus Rößiger, Zoi Saxonis, Reinhard Marks, Rebecca Wurm-Kuczera, Markus Maulhardt, Franziska Brunner, Peter Dreger, Udo Holtick, Stephanie Mayer, Francis Ayuketang Ayuk, Karin Schmitz, Georg Lenz, Belana Kuhn, Ulrike Kolar-Michaelis, Friedrich Gregor, Débora-Michèle Grote Urtubey
article en

Abstract

For patients with large B-cell lymphoma progressing after multiple lines of therapy few treatment options remain, including the new CD19-directed antibody-drug conjugate loncastuximab tesirine (lonca). To further elucidate its efficacy and safety, we conducted a real-world analysis including data from 31 German centers. Ninety-three heavily pre-treated patients received lonca in third and later line of therapy. 76% had received treatment with chimeric antigen receptor T-cells (n=55), bispecific antibodies (BsAbs) (n=56) or both (n=40). The overall response rate was 27% and complete response rate was 10%. Median progression-free (mPFS) and overall survival (mOS) were 2.2 and 4.4 months, respectively. Median PFS of responders was 11.4 months. Toxicity was acceptable, with grade ≥ 3 infections (13%) being the most common adverse event. Patients receiving subsequent allogeneic stem cell transplantation survived significantly better than the remaining non-consolidated patients (mOS: 15.2 vs. 3.8 months, p=0.048). In multivariable analysis, no response to the last therapy prior to lonca (OS - HR: 2.5, p=0.014) and secondary IPI (PFS/OS - HR: ≥2.0, p≤0.024) were significantly associated with poor outcomes. Lonca demonstrated a favorable safety profile with moderate efficacy in heavily pretreated patients. While enabling timely access to subsequent therapy, efficacy in earlier lines with combination partners may further increase response rates and durability of response.

Blood Advances
Universität Hamburg (DE), University of Freiburg (DE), University of Cologne (DE), Heidelberg University (DE), University Medical Center Freiburg (DE), University Hospital Augsburg (DE), University Hospital Heidelberg (DE), University Medical Center (US), LMU Klinikum (DE), University Hospital Regensburg (DE), Medizinische Hochschule Hannover (DE), Universitätsklinikum Erlangen (DE), Düsseldorf University Hospital (DE), University Hospital Münster (DE), Evangelisches Krankenhaus Bielefeld (DE), University Medical Center Hamburg-Eppendorf (DE), Klinikum Oldenburg (DE), University Hospital Schleswig-Holstein (DE), Essen University Hospital (DE), University Hospital Leipzig (DE), RoMed Kliniken (DE), Marien Hospital Düsseldorf (DE), Jena University Hospital (DE), DIAKO (DE), University Hospital Cologne (DE), University Hospital Ulm (DE), Helios Hospital Berlin-Buch (DE), West German Heart and Vascular Center Essen (DE), Klinikum Chemnitz (DE), Johannes Wesling Klinikum Minden (DE), Agaplesion Diakonieklinikum Rotenburg (DE), Heinrich Heine University Düsseldorf (DE), Franklin University (US), Martin Luther University Halle-Wittenberg (DE), Ludwig-Maximilians-Universität München (DE), Saarland University (DE), University of Lübeck (DE), Otto-von-Guericke-Universität Magdeburg (DE)
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Lymphoma Diagnosis and Treatment
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