ESTRO 2021 Abstract Book

S895

ESTRO 2021

USA; 4 H. Lee Moffitt Cancer Center and Research Institute, Department of Malignant Hematology, Tampa, USA; 5 H. Lee Moffitt Cancer Center and Research Institute, Department of Bone and Marrow Transplant and Cellular Immunotherapy, Tampa, USA Purpose or Objective Relapsed/refractory (R/R) mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma with a historically poor prognosis. CAR-T cell therapy for R/R MCL lead to high response rates and FDA approval of brexucabtagene autoleucel for R/R MCL. Autologous CAR T cell therapy consists of a manufacturing period lasting 3-5 weeks, during which “bridging” therapy is often provided to reduce or stabilize disease prior to CAR T cell infusion. We have previously reported on bridging radiotherapy (RT) in large cell lymphoma prior to CAR T cell therapy, but its role and toxicity profile in this setting are currently unknown. Notably, bridging RT was not allowed on the ZUMA-2 trial with brexucabtagene autoleucel approval. Materials and Methods We performed a retrospective review from 2 academic centers to identify R/R MCL recipients of bridging RT prior to brexucabtagene autoleucel. Bridging RT was defined as MCL-directed RT delivered within 3 months of CAR T cell infusion. We identified patient characteristics, treatment-related toxicities, and clinical outcomes. RT treatment plans were compared to subsequent imaging to identify recurrence patterns and time to events. Results From 7/2020-12/2020, we identified seven patients treated with bridging RT. Median age was 65 (range 55- 80). The majority of patients were male (n=6, 86%), had Stage IV (n=6, 86%) disease, and had undergone a median of 4 prior lines of therapy (range 1-7). Median Mantle Cell Lymphoma International Prognostic Index Score (MIPI) at time of apheresis was 7.3 (range 5.3-8.5). Among the seven patients, 12 sites of disease, of which one was bulky (>10cm) and four were extranodal, were treated with bridging RT to a median dose of 20Gy. The most common schedules were 4Gy in 2 fractions (n=3), 20Gy in 10 fractions (n=2), and 20Gy in 5 fractions (n=2). No patient had grade 3 or higher CRS and two patients had grade 3 CRES. Four patients (57%) received administration of tocilizumab and steroids. There were no toxicities occurring within the radiation field after CAR T cell infusion. At a median follow-up of 4.7 months, all the patients continue to be alive with two patients developing disease progression. One patient relapsed with a new lesion outside of the bridging RT field without any progression in-field. The other patient progressed in-field at three distinct disease sites that were each previously treated with 4Gy in 2 fractions as bridging therapy. No other disease sites treated with bridging RT experienced a local failure. Conclusion In this first report describing the experience of patients receiving bridging RT prior to CAR T-cell therapy for R/R MCL, no excessive and/or severe toxicities were observed. Thus, RT warrants further evaluation as a bridging treatment strategy prior to CAR T cell therapy in MCL. PO-1076 Hypofractionated Total Marrow Irradiation in second allogeneic hematopoietic stem cell transplantats S. Vagge 1 , D. Esposito 2 , D. Tramontano 2 , R. Corvò 3 , E. Angelucci 4 , A. Dominietto 4 1 IRCCS Ospedale Policlinico San Martino, Radiation Oncology, Genova, Italy; 2 IRCCS Ospedale Policlinico san Martino, and DISSAL Unige, Radiation Oncology, Genova, Italy; 3 IRCCS Ospedale Policlinico San Martino, and DISSAL Unige, Radiation Oncology, Genova, Italy; 4 IRCCS Ospedale Policlinico San Martino, Hematology, Genova, Italy Purpose or Objective Relapse after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with poor outcomes. A second myeloablative conditioning regimen is crucial for disease control, but the risk of transplant mortality due to toxic complications is very high. Herein we report the preliminary results of a pilot study designed to fit a modern Total Marrow Irradiation (TMI) alternative to a conditioning regimen with standard Total Body Irradiation (TBI). In our proposal, we also investigate the feasibility of whole marrow re-irradiation after previous TBI. Materials and Methods Eleven patients with acute leukemia relapsed after a first allogeneic HSCT were treated with daily single fraction TMI during the conditioning regimen for the second allogeneic HSCT. The donor was haploidentical for 9 patients, unrelated and HLA-identical sibling for two patients. The choice of TMI fraction dose of 4 Gy, up to 12 Gy, instead of the conventional 2 Gy, potentially enhanced the biologically effective dose approximately from 20% to 60%, considering alpha/beta ratio between 10-1.49. In comparison, the total dose of 8 Gy in 2 fractions schedule is potentially equivalent to the conventional 12 Gy in six fractions of TBI (only for the low alpha/beta ratio). The conditioning regimen was: TMI 12 Gy in 6 patients or TMI 8 Gy in 5 patients with low- performance status, plus thiotepa, fludarabine, Alkeran. All the TMI were performed by Helical Tomotherapy or by Radixact system. Daily whole-body image-guided verified the setup system. Graft versus host disease (GvHD) prophylaxis for SIB and UD consisted of cyclosporine methotrexate and ATG, whereas for HAPLO, it was high dose post-transplant cyclophosphamide (PT-CY), cyclosporine, and mycophenolate. Results The median Planning Treated Volume (PTV) was 10499 cc, median patient's height (from vertex to knees) was 111 cm, and the median treatment time was strictly related to the target's length, which was 2310 seconds. The median age was 45 years (range, 19-70 years); 3 patients were in remission, 8 had active disease at the time of the second allogeneic HSCT, and 3 patients had been previously treated with myeloablative 12 Gy TBI regimen during their first allo-HSCT. The median time from the first TBI was 10 years. With a median follow- up of 610 days (range 227-910), the cumulative incidence of transplant-related mortality was 22%. The relapse rate was 22%, and the two patients who died of leukemia were not in remission at the transplant time. The actuarial 21 months disease free-survival (DFS) was 52%. The cumulative incidence of grade I II acute GVHD