1089 - Radiation Therapy for Bridging to CD19 CAR T-Cell Therapy for Large B-Cell Lymphoma - A Multicenter Analysis by the GoCART Coalition and the EBMT Lymphoma Working Party
Presenter(s)
M. Oertel1, P. Berning2, C. Peczynski3, E. Michel3, F. Imran3, R. Sanderson4, D. Taurino5, P. Dreger6, E. Galli7, R. Ram8, P. Vandenberghe9, I. Cutini10, F. Sillito11, U. Novak12, D. Beauvais13, R. Noel14, A. Bazarbachi15, G. Lenz2, H. T. T. Eich1, and N. Schmitz2; 1Department of Radiation Oncology, University Hospital Muenster, Muenster, Germany, 2Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany, 3European Society for Blood and Marrow Transplantation, Paris, France, 4King's College NHS Trust, London, United Kingdom, 5IRCCS Humanitas Research Hospital, Humanitas, Cancer Center, Milano, Rozzano Milano, Milan, Italy, 6Department of Medicine V, University of Heidelberg, Heidelberg, Germany, 7Dipartimento di Scienze di laboratorio ed ematologiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy, 8Hematology Department-Tel Aviv (Sourasky) Medical Center, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel, 9Department of Hematology, University Hospitals Leuven, Leuven, Belgium, 10SOD Ematologia, AOU Careggi, Florence, Italy, 11Department of Haematology, University College London (UCL) Hospitals NHS Foundation Trusts, London, United Kingdom, 12Department of Medical Oncology, Inselspital, University Hospital and University of Bern, Bern, Switzerland, 13Department of Hematology, CHU Lille, Lille, France, 14Programme de Transplantation & Thérapie Cellulaire, Marseille, France, 15Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
Purpose/Objective(s): Chimeric antigen receptor T-cell therapy (CART) is an effective treatment option for patients with large B-cell lymphoma (LBCL). Bridging therapies (BT) after leukapheresis are frequently used to reduce tumor burden and prevent progression before CAR T re-infusion. The role of radiotherapy (RT) is incompletely described.
Materials/Methods: Data were collected retrospectively by the GoCART coalition and the EBMT lymphoma working party. Eligible for this analysis were adult patients with LBCL who received RT (± corticosteroids) for bridging prior to axicabtagene ciloleucel (axi-cel) or tisagen lecleucel (tisa-cel) between 2018 and July 2023.
Results: In total, 129 patients had RT alone for bridging and were included in the analysis. RT patients had a median age of 57.9 years, mostly suffered from DLBCL, NOS (89.1 %) and had an ECOG performance status at diagnosis of 0-1 (91.3 %). Prior RT had been used in 36.2 % of patients and 34.4 % underwent =3 prior therapy lines. Median RT total dose was 30 Gy (IQR: 30-36 Gy, 54 missing), the predominant locations (available for 69 patients) were the abdomen/retroperitoneum/mesenteric (n=14) and mediastinum (11). At lymphodepletion, RT patients showed stage III-IV, bulk, elevated LDH, and IPI =2 in 60.7 %, 19.7 %, 31.4 % and 41.5 % of cases. At leukapheresis, 92.9 % of patients had stable disease or progression (SD/PD), 5.6 % were in partial remission (PR), only 1.6 % were in complete remission (CR). Respective percentages at lymphodepletion were 63.5 %, 27.0 %, and 9.5 % for SD/PD, PR and CR. Thus, RT resulted in an improvement of disease status in 31.5 % of patients (64.5 % showed no change, 4.0 % of patients progressed). Axi-cel was used in 62.8 %, tisa-cel in 37.2 % of cases. With a median follow-up of 30 months, relapse incidence, progression-free and overall survival were 39.9 %, 50.5 % and 56.7 % at 30 months after CAR-T cell infusion. RT toxicities were manageable with incidence of grade 3-4 infections of 26 % at 30 months, incidence of 15 day CRS of 89.7 % (12.4 % grades 3-4) and incidence of 15 day ICANS of 25.6 % (34.4 % grades 3-4). Non-relapse mortality and incidence of secondary malignancy were 9.6 % and 2.8 %, respectively, after 30 months.
Conclusion: In this large multicenter analysis, RT used for bridging to CART resulted in considerable response rates and durable remissions after CART. Details of RT and patient characteristics will be presented.