Real-world use of loncastuximab tesirine in heavily pretreated and high risk relapsed/refractory large B-cell lymphoma patients: German multicenter analysis
Abstract
Abstract Patients (pts) with large B-cell lymphoma (LBCL) relapsing or being refractory (r/r) following two prior systemic therapies are particularly difficult to treat. CD19-directed antibody-drug conjugate loncastuximab tesirine (lonca) represents one of the treatment options for these pts. In the LOTIS-2 trial lonca showed promising efficacy data with an overall response rate (ORR) of 48.3% and a complete response rate (CRR) of 24%. In the real-world setting in Europe, data on the efficacy and safety of lonca are scarce to date. To assess the efficacy and feasibility of lonca we conducted a retrospective, multicenter analysis, enrolling 72 pts with r/r LBCL treated with lonca as a single agent in 24 centers from Germany. We included de novo diffuse large B-cell lymphoma (DLBCL) (40/72), high grade B-cell lymphoma (HGBL) [(17/72; MYC & BCL2 rearrangements (11/17); not otherwise specified (NOS) (6/17)], transformed indolent lymphoma (14/72) and T-cell/histiocyte-rich large B-cell lymphoma (TCRLBCL) (1/72). Median age at lonca initation was 62 with almost equal gender distribution. Pts were heavily pretreated: 28 pts (38%) and 33 pts (46%) underwent lonca in forth line (4L) or later (5L+); only 11 pts (15%) received lonca in third line (3L). Seventy seven% pts were refractory to the last therapy prior lonca while 71% pts presented with IPI ≥ 3, 36% pts with bulky disease (≥ 7.5 cm) and 15% pts with ECOG 3-4 at lonca initiation. Of pts receiving lonca in 3L, 45% had bulky disease and IPI ≥ 3, 63% had a primary refractory or early relapsed disease after first line therapy. Finally, 43 pts (60%) had prior CAR-T treatment and 50 pts (69%) had prior bispecific antibodies (BsAb). Just 10% of pts (7/72) had no prior exposure to either CAR-T or BsAb. Of 72 pts, 20 received lonca with intent to consolidate with CAR-T cell therapy (14/20) or allogeneic stem cell transplantation (allo-SCT) (6/20). Infections were documented in 31% of pts, with grades 3 in 13% of all pts. The incidence of liver enzyme elevation was 28% with only 1 grade 3 (1.3%). The frequency of edema was 13% with two pts suffering from grade 3. Skin reactions occurred in 14% of pts (all grades 1-2). Anemia, leukopenia and thrombocytopenia grade ≥3 were documented in 15%, 21% and 29% of pts, respectively. Overall, 24% of pts responded to lonca, with 6% achieving CR and 18% partial response (PR). The ORR did not differ significantly in lonca administered in 3L, 4L, or 5L+: 18% vs. 21% vs. 27% (p=0.779). Similarly, ORR was 21% and 25% (p=0.728) in CAR-T naive/pretreated, and 23% and 24% (p=0.9) in BsAb naive/pretreated pts. Lonca was associated with numerically higher ORR in pts treated with intent to bridge (30% vs. 21%; p=0.429) and significantly higher in those pts (9/20) who underwent subsequent consolidation with CAR-T or allo-SCT: 56% vs. 20% without consolidation (p=0.017). The median progression-free survival (mPFS) was 2.1 months (mo), and the median overall survival (mOS) was 3.7 mo, while being significantly higher in responders (mPFS 7.2 mo; mOS 8.6 mo; p≤0.002 for both). Finally, pts achieving CR showed significantly higher PFS and OS rates than those in PR: mPFS 13.7 vs. 4.6 mo (p=0.037) and mOS 14.9 vs. 5.2 (p=0.012). In the multivariate analysis, ECOG at lonca administration (PFS - [HR=2.09, p=0.042]) and LDH at the time of lonca considered as continuous variable (p=0.01 for OS) were the strongest predictors of survival after initiation of lonca. In this real-world cohort representing a particularly difficult-to-treat population, with almost half of pts treated in 5L+, lonca as a single-agent showed a response rate of roughly 25% in r/r LBCL pts with a low CR rate due to a high proportion of pts who were high risk and heavily pretreated. The safety profile observed was consistent with known toxicities and was manageable in routine clinical practice with no new signals detected. Lonca is currently explored in earlier lines and in combination in ongoing clinical studies.
Article Details
Authors (52)
Evgenii Shumilov
1University Hospital Muenster, Department of Medicine A, Hematology, Oncology and Pneumology, Muenster, Germany
Débora-Michèle Grote Urtubey
2University Hospital Muenster, Department of Nuclear Medicine, Muenster, Germany
Marcel Teichert
1Department of Hematology and Stem Cell Transplantation, West German Cancer Center and German Cancer consortium (DKTK partner site Essen), University Hospital Essen, University of Duisburg-Essen, Essen, Germany, Essen, Germany
Maximilian Seib
1University Hospital Muenster, Department of Medicine A, Hematology, Oncology and Pneumology, Muenster, Germany
Rebecca Wurm-Kuczera
Department of Hematology, Oncology and Tumor Immunology, Charité University Medical Center
Joseph Kauer
14Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany, Heidelberg, Germany
Friedrich-Linus Roessiger
9UK Erlangen-Nuremberg, Erlangen, Germany
Tobias Tix
7Department of Medicine III, Hematology/Oncology, LMU University Hospital, LMU Munich, Munich, Germany
Alexander Hölscher
8Department of Hematolgy, Oncology and Immunolgy, University Hospital of Duesseldorf, Duesseldorf, Germany
Philipp Gödel
1University Hospital Cologne, Department of Internal Medicine I, Cologne, Germany
Christoph Brey
10Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Paolo Mazzeo
1University Medical Center Göttingen, Department of Hematology and Medical Oncology, Göttingen, Germany
Zoi Saxonis
6Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Dept. of Hematology, Stem Cell Transplantation, Oncology and Palliative Medicine, CVK, Berlin, Germany
Belana Kuhn
3Department of Hematology and Stem Cell Transplantation, West German Cancer Center and German Cancer consortium (DKTK partner site Essen), University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Vanja Zeremski
13Department of Hematology and Oncology, Medical Center, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
Franziska Brunner
14Department of Internal Medicine IV, Hematology and Oncology, Martin Luther University Halle-Wittenberg, Halle, Germany
Susanne Ghandili
4University Hospital Hamburg Eppendorf, Department of Hematology and Oncology, Hamburg, Germany
Enver Aydilek
11Department of Hematology and Medical Oncology, University Hospital Goettingen, Goettingen, Germany
Markus Maulhardt
1University Medical Center Göttingen, Department of Hematology and Medical Oncology, Göttingen, Germany
Philipp Nakov
6University Hospital Schleswig-Holstein, Department of Internal Medicine II, Kiel, Germany
Gregor Friedrich
18Department of Hematology, Cell Therapy, Hemostaseology and Infectious Diseases, University Hospital Leipzig, Leipzig, Germany
Christian Schultze-Florey
10Hannover Medical School, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover, Germany
Giuliano Filippini Velazquez
6Department of Hematology, University Hospital Augsburg, Augsburg, Germany
Igor Age Kos
Anna Ossami Saidy
21Department of Hematology and Cell Therapy Helios Klinikum Berlin-Buch, Berlin, Germany
Christoph Kimmich
23Department of Hematology and Oncology, University Hospital Oldenburg, Oldenburg, Germany
Maika Klaiber-Hakimi
19Marien Hospital Düsseldorf, Clinic for Hematology, Oncology and Palliative Care, Düsseldorf, Germany
Philipp Berning
1Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, United States
Andrea Kerkhoff
7Medizinische Klinik A, University Hospital Münster, Münster, Germany
Bertram Glass
21Department of Hematology and Cell Therapy Helios Klinikum Berlin-Buch, Berlin, Germany
Isabelle Krämer
14Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany, Heidelberg, Germany
Lorenz Thurner
Mathias Lutz
20Department of Hematology, University Hospital Augsburg, Augsburg, Germany
Florian Heidel
Vladan Vucinic
15University Hospital Leipzig, Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, Leipzig, Germany
Christiane Pott
6University Hospital Schleswig-Holstein, Department of Internal Medicine II, Kiel, Germany
Andreas Viardot
24University Hospital of Ulm, Ulm, Germany
Gerald Wulf
1University Medical Center Göttingen, Department of Hematology and Medical Oncology, Göttingen, Germany
Thomas Weber
Dimitrios Mougiakakos
Francis Ayuk
From the Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Udo Holtick
2University Hospital Cologne, Cologne, Germany
Sascha Dietrich
Niklas Gebauer
17University Hospital Schleswig-Holstein, Campus Luebeck, Department for Hematology and Oncology, Lübeck, Germany
Ulf Schnetzke
2Klinik für Innere Medizin II, Abteilung für Hämatologie und Iinternistische Onkologie, Universitätsklinikum Jena, Jena, Germany
Mathias Hänel
7Department III of Internal Medicine, Klinikum Chemnitz, Chemnitz, Germany
Martin Dreyling
LMU Hospital, Munich, Germany
Peter Dreger
Björn Chapuy
Department of Hematology, Oncology and Tumor Immunology, Charité University Medical Center
Fabian Müller
Friedrich-Alexander-Universität Erlangen–Nürnberg, Erlangen, Germany
Bastian von Tresckow
1Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, and German Hodgkin Study Group, Cologne, Germany
Georg Lenz