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