ESTRO 2023

Session Item

Monday

May 15

16:00 - 17:00

Stolz 1

Sarcoma - Haematology

Chair: Falk Röder, Austria;

Chair: , Austria

Session Code: 3502

Session Type: Mini-Oral

Track: Clinical

16:00 - 17:00

A multicentric retrospective analysis of the potential synergy between radiotherapy and CAR T-cells

Christian Baues, Germany

Presentation Number: MO-0952

Abstract

Abstract Title:

A multicentric retrospective analysis of the potential synergy between radiotherapy and CAR T-cells

Authors:

Jiaqi Fan¹, Anne Adams², Noëlle Sieg³, Jan-Michel Heger⁴, Philipp Gödel⁵, Nadine Kutsch⁴, David Kaul⁶, Marcel Teichert⁷, Bastian von Tresckow⁷, Veit Bücklein⁸, Gretha Goesmann⁹, Minglun Li⁹, Nathalie Struve¹, Maike Trommer¹⁰, Philipp Linde¹, Johannes Rosenbrock¹, Eren Celik¹, Olaf Penack¹¹, Martin Stuschke¹², Marion Subklewe⁸, Claus Belka⁹, Michael von Bergwelt-Baildon⁸, Peter Borchmann¹³, Simone Marnitz¹, Christian Baues¹⁴

¹Department of Radiation Oncology and Cyberknife Center, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; ²Institute of Medical Statistics and Computational Biology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; ³Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Cologne Lymphoma Working Group (CLWG), Cologne, Germany; ⁴Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany, Cologne Lymphoma Working Group (CLWG), Cologne, Germany; ⁵Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany, , Cologne Lymphoma Working Group (CLWG), Cologne, Germany; ⁶Department for Radiation Oncology, Charité School of Medicine and University Hospital Berlin, Berlin, Germany; ⁷Department of Hematology and Oncology, University Hospital Essen, Essen, Germany; ⁸Department of Hematology and Oncology, University Hospital Munich (LMU Munich), Munich, Germany; ⁹Department of Radiation Oncology, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany; ¹⁰Department of Radiation Oncology and Cyberknife Center, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany, Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne, and Düsseldorf, Germany; Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; ¹¹Charité – 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; ¹²Department of Radiation Oncology, West German Cancer Center, Medical Faculty, University Hospital Essen, Essen, Germany; ¹³Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany;, Cologne Lymphoma Working Group (CLWG), Cologne, Germany; ¹⁴Department of Radiation Oncology and Cyberknife Center, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany, Cologne Lymphoma Working Group (CLWG), Cologne, Germany

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Purpose or Objective

Chimeric antigen receptor (CAR) T-cell therapy has improved the very limited overall survival (OS) of patients with intensively pretreated hematologic malignancies. However, more than 50% of the patients experience again disease progression and have then a very poor outcome. As suggested by previous analyses, Radiotherapy (RT) in combination with CAR T-cells may have an immunomodulatory effect without increased treatment-related toxicity. In the current multicentric retrospective analysis, we investigated the potentially synergistic effects of RT and CAR T-cells.

Material and Methods

Of 89 patients from four academic centers who received CAR T-cell therapy mostly for diffuse large B-cell lymphoma (DLBCL), 44 patients underwent bridging RT (22) or received salvage RT (22).

Results

RT, with a median dose of 35.5 Gy, was well tolerated. A trend of improved OS was observed in the entire cohort with RT vs. without RT (HR 0.61, p=0.10), and a significantly improved OS in irradiated patients within the subgroup of DLBCL (p=0.01). In the subgroup of localized DLBCL relapse after CAR T-cell therapy, patients receiving salvage therapy including RT also had an improved OS after disease progression vs. patients without RT (1-year OS rate 89% vs. 38%, p= 0.03). RT in combination with CAR T-cells led neither to an increased rate of toxicity nor to a decreased response rate.

Conclusion

Our analysis demonstrated that RT in combination with CAR T-cells led to an improved OS in patients with DLBCL, especially in those patients with localized DLBCL relapse after CAR T-cell therapy failure without increased treatment-related toxicity. This could be due to an enhanced local anti-tumor effect of CAR T-cells from RT sensitizing. Further clinical investigations are needed to clarify the optimal subgroups of patients, the RT field, and the timing of RT.