Potential synergy between radiotherapy and CAR T-cells – A multicentric analysis of the role of radiotherapy in the combination of CAR T cell therapy.

Feb 27, 2023

Experts: Jiaqi Fan,Anne Adams,Noëlle Sieg,Jan-Michel Heger,Philipp Gödel,Nadine Kutsch,David Kaul,Marcel Teichert,Bastian von Tresckow,Veit Bücklein,Gretha Goesmann,Minglun Li,Nathalie Struve,Maike Trommer,Philipp Linde,Johannes Rosenbrock,Eren Celik,Olaf Penack,Martin Stuschke,Marion Subklewe,Claus Belka,Michael von Bergwelt-Baildon,Peter Borchmann,Simone Marnitz,Christian Baues

Chimeric antigen receptor (CAR) T-cell therapy has improved the limited overall survival (OS) of patients with intensively pretreated diffuse large B-cell lymphoma (DLBCL). However, the potentially life-threatening toxicities of CAR T-cells and early relapses remain a challenge. As suggested by smaller monocentric analyses, radiotherapy (RT) in combination with CAR T-cells may have an immunomodulatory effect. Method/ Results: In this multicentric retrospective analysis, we investigated potentially synergistic effects of RT and CAR T-cells. Of 78 patients from four centers who received CAR T-cell therapy for DLBCL, 37 patients underwent bridging RT or received salvage RT. RTs (median 36 gray) were well tolerated. Therapy response and disease control of CAR T-cell therapy were comparable after bridging RT or bridging systemic therapy. High-grade neurotoxicity tended to occur less frequently after bridging RT. After further disease progression, patients with localized relapses showed better outcomes, compared to those in advanced stage. In the subgroup with localized relapse, patients receiving salvage RT had an increased OS, vs. those without salvage RT (1-year OS rate 89% vs. 38%, p=0.03). Conclusion Our analysis demonstrated that RT in combination with CAR T-cells led neither to high-grade toxicities, nor to a decreased response rate. We observed better outcomes of salvage therapies in patients with localized relapses vs. those with advanced stage relapses. Especially the patients who received salvage RTs for localized relapses seem to benefit more. Further analyses are necessary to clarify whether specific synergistic effects exist, such as an enhanced anti-tumor effect of CAR T-cells from RT sensitizing.
Copyright © 2023 Elsevier B.V. All rights reserved.

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ABOUT THE EXPERTS

Jiaqi Fan,Anne Adams,Noëlle Sieg,Jan-Michel Heger,Philipp Gödel,Nadine Kutsch,David Kaul,Marcel Teichert,Bastian von Tresckow,Veit Bücklein,Gretha Goesmann,Minglun Li,Nathalie Struve,Maike Trommer,Philipp Linde,Johannes Rosenbrock,Eren Celik,Olaf Penack,Martin Stuschke,Marion Subklewe,Claus Belka,Michael von Bergwelt-Baildon,Peter Borchmann,Simone Marnitz,Christian Baues

Jiaqi Fan

Department of Radiation Oncology and Cyberknife Center, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Anne Adams

Institute of Medical Statistics and Computational Biology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Noëlle Sieg

Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Germany; Cologne Lymphoma Working Group (CLWG), Cologne, Germany.

Jan-Michel Heger

Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Germany; Cologne Lymphoma Working Group (CLWG), Cologne, Germany.

Philipp Gödel

Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Germany; Cologne Lymphoma Working Group (CLWG), Cologne, Germany.

Nadine Kutsch

Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Germany; Cologne Lymphoma Working Group (CLWG), Cologne, Germany.

David Kaul

Department for Radiation Oncology, Charité School of Medicine and University Hospital Berlin, Berlin, Germany.

Marcel Teichert

Department of Hematology and Oncology, University Hospital Essen, Essen, Germany.

Bastian von Tresckow

Department of Hematology and Oncology, University Hospital Essen, Essen, Germany.

Veit Bücklein

Department of Hematology and Oncology, University Hospital Munich (LMU Munich), Munich, Germany.

Gretha Goesmann

Department of Radiation Oncology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Minglun Li

Department of Radiation Oncology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Nathalie Struve

Department of Radiation Oncology and Cyberknife Center, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Maike Trommer

Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Germany; Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Philipp Linde

Department of Radiation Oncology and Cyberknife Center, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Johannes Rosenbrock

Department of Radiation Oncology and Cyberknife Center, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Eren Celik

Department of Radiation Oncology and Cyberknife Center, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Olaf Penack

Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Tumorimmunology, Augustenburger Platz 1, 13353 Berlin, Germany.

Martin Stuschke

Department of Radiation Oncology, West German Cancer Center, Medical Faculty, University Hospital Essen, Essen, Germany.

Marion Subklewe

Department of Hematology and Oncology, University Hospital Munich (LMU Munich), Munich, Germany.

Claus Belka

Department of Radiation Oncology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

Michael von Bergwelt-Baildon

Department of Hematology and Oncology, University Hospital Munich (LMU Munich), Munich, Germany.

Peter Borchmann

Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Germany; Cologne Lymphoma Working Group (CLWG), Cologne, Germany.

Simone Marnitz

Department of Radiation Oncology and Cyberknife Center, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Christian Baues

Department of Radiation Oncology and Cyberknife Center, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Cologne Lymphoma Working Group (CLWG), Cologne, Germany. Electronic address: christian.baues@uk-koeln.de.