Polatuzumab vedotin as a salvage and bridging treatment in relapsed or refractory large B-cell lymphomas

Author:

Liebers Nora12,Duell Johannes3,Fitzgerald Donnacha14ORCID,Kerkhoff Andrea5,Noerenberg Daniel6,Kaebisch Eva6ORCID,Acker Fabian7ORCID,Fuhrmann Stephan8ORCID,Leng Corinna9,Welslau Manfred10,Chemnitz Jens11,Middeke Jan-Moritz12,Weber Thomas13ORCID,Holtick Udo14,Trappe Ralf15,Pfannes Roald16,Liersch Ruediger17,Spoer Christian18,Fuxius Stefan19,Gebauer Niklas20,Caillé Léandra1,Geer Thomas21,Koenecke Christian22ORCID,Keller Ulrich9ORCID,Claus Rainer23ORCID,Mougiakakos Dimitrios24,Mayer Stephanie25,Huettmann Andreas26ORCID,Pott Christiane27,Trummer Arne28,Wulf Gerald29,Brunnberg Uta7,Bullinger Lars6,Hess Georg30,Mueller-Tidow Carsten12,Glass Bertram8,Lenz Georg5,Dreger Peter1,Dietrich Sascha124

Affiliation:

1. Department of Medicine V, Heidelberg University Hospital, Heidelberg, Germany;

2. National Center for Tumor Diseases Heidelberg, Heidelberg, Germany;

3. Department of Internal Medicine II, Würzburg University Hospital, University of Würzburg, Würzburg, Germany;

4. European Molecular Biology Laboratory, Heidelberg, Germany;

5. Department of Medicine A, University Hospital Münster, Münster, Germany;

6. Department of Hematology, Oncology and Tumor Immunology (Campus Virchow-Klinikum), Charité University Medicine, Berlin, Germany;

7. Department of Medicine 2, Hematology and Oncology, University Hospital Frankfurt, Frankfurt, Germany;

8. Department of Hematology, HELIOS Klinikum Berlin-Buch, Berlin, Germany;

9. Department of Hematology, Oncology, and Tumor Immunology (Campus Benjamin Franklin), Charité University Medicine, Berlin, Germany;

10. MVZ am Klinikum Aschaffenburg, Onkologie und Hämatologie, Aschaffenburg, Germany;

11. Gemeinschaftsklinikum Mittelrhein GmbH, Koblenz, Germany;

12. University Hospital Dresden, Dresden, Germany;

13. Department of Medicine IV, Hematology and Oncology, University of Halle, Halle, Germany;

14. Department I of Internal Medicine, Medical Faculty and University Hospital, Cologne, University of Cologne, Cologne, Germany;

15. Department of Hematology and Oncology, DIAKO Ev. Diakonie-Krankenhaus Bremen, Bremen, Germany;

16. Department of Medicine I, Städtisches Klinikum Dessau, Dessau, Germany;

17. Praxis Medical Center, Gemeinschaftspraxis für Hämatologie und Onkologie Münster, Münster, Germany;

18. MVZ am EVK Düsseldorf, Internistische Onkologie und Hämatologie, Düsseldorf, Germany;

19. Onkologische Schwerpunktpraxis Heidelberg, Heidelberg, Germany;

20. Department of Haematology and Oncology, University Hospital of Schleswig-Holstein, Campus Lübeck, Germany;

21. Diakonie Klinikum Schwäbisch-Hall, Innere Medizin III, Schwäbisch Hall, Germany;

22. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany;

23. Hematology and Oncology, Medical Faculty, University of Augsburg, Augsburg, Germany;

24. Department of Internal Medicine 5, Hematology and Clinical Oncology, Friedrich-Alexander University (FAU) of Erlangen-Nuremberg, Erlangen, Germany;

25. Department of Internal Medicine III, University Hospital of Regensburg, Regensburg, Germany;

26. Department of Hematology, University Hospital of Essen, Essen, Germany;

27. Second Medical Department, University Hospital Schleswig-Holstein, Campus Kiel, Germany;

28. Department of Hematology and Oncology, Klinikum Braunschweig, Braunschweig, Germany;

29. Clinic for Hematology and Medical Oncology, University Medicine Göttingen, Germany; and

30. Department of Hematology, Oncology and Pneumology, Johannes Gutenberg-University, Mainz, Germany

Abstract

The antibody-drug conjugate polatuzumab vedotin (pola) has recently been approved in combination with bendamustine and rituximab (pola-BR) for patients with refractory or relapsed (r/r) large B-cell lymphoma (LBCL). To investigate the efficacy of pola-BR in a real-world setting, we retrospectively analyzed 105 patients with LBCL who were treated in 26 German centers under the national compassionate use program. Fifty-four patients received pola as a salvage treatment and 51 patients were treated with pola with the intention to bridge to chimeric antigen receptor (CAR) T-cell therapy (n = 41) or allogeneic hematopoietic cell transplantation (n = 10). Notably, patients in the salvage and bridging cohort had received a median of 3 prior treatment lines. In the salvage cohort, the best overall response rate was 48.1%. The 6-month progression-free survival and overall survival (OS) was 27.7% and 49.6%, respectively. In the bridging cohort, 51.2% of patients could be successfully bridged with pola to the intended CAR T-cell therapy. The combination of pola bridging and successful CAR T-cell therapy resulted in a 6-month OS of 77.9% calculated from pola initiation. Pola vedotin-rituximab without a chemotherapy backbone demonstrated encouraging overall response rates up to 40%, highlighting both an appropriate alternative for patients unsuitable for chemotherapy and a new treatment option for bridging before leukapheresis in patients intended for CAR T-cell therapy. Furthermore, 7 of 12 patients with previous failure of CAR T-cell therapy responded to a pola-containing regimen. These findings suggest that pola may serve as effective salvage and bridging treatment of r/r LBCL patients.

Publisher

American Society of Hematology

Subject

Hematology

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