3699 - Bridging Radiation Durably Controls Patients with Bulky Tumors Treated with CAR-T Cell Therapy
Presenter(s)
R. R. Patel1, A. Tward2, B. Fregonese1, N. P. Mankuzhy1, K. Lapen1, G. Cederquist1, Z. R. Moore1, A. Dreyfuss1, A. Boardman3, P. B. Dahi3, R. J. Lin3, M. Scordo3, G. L. Shah3, G. Salles4, M. L. Palomba3, M. A. Perales3, R. Shouval3, J. Yahalom1, and B. S. Imber1; 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 2Columbia University College of Physicians and Surgeons, New York, NY, United States, 3Department of Medicine, Bone Marrow Transplant Division, Memorial Sloan Kettering Cancer Center, New York, NY, 4Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Purpose/Objective(s): Bridging radiotherapy (BRT) is well-established for cytoreduction prior to CD19 chimeric antigen receptor T-cell therapy (CAR-T). Metabolic tumor volume (MTV) reduction has shown to improve outcomes. Bulky tumors remain a challenge to treat given high MTV and lower CAR-T penetration. Tumor bulk predicts for worse prognosis, however unique outcomes are not well characterized independently from broader series. We sought to report bulk focused outcomes of BRT specific to this high-risk group.
Materials/Methods: We identified patients with B-cell malignancies treated with BRT between 2016-2024. All were irradiated to =1 site of bulky disease, defined as a tumor or conglomerate with a maximal dimension =7.5cm. Response was determined by Lugano criteria. Cox regression testing was used for statistical comparison.
Results: Of 116 patients who received BRT, we identified 31 patients treated to 33 bulky sites. Median follow up was 13 months. Most had diffuse large B-cell histology (94%). Prior to BRT, patients had limited site disease (1-3 PET avid sites, 55%) or more extensive disease (>3 sites, 45%). The most common BRT regimens were 30Gy/10 (41%) and 36Gy/12 (19%), with total doses ranging from 7.5-54Gy. Systemic bridging therapy was also given in 18 patients (58%). Patients received Axicabtagene (45%), Lisocabtagene (22%), Tisagenlecleucel (19%), or an investigational agent (13%).
Median tumor size and SUV prior to BRT were 9.5cm (range 7.8-19.9cm) and 20.5 (3.4-43.8), respectively. Twelve-month LC, PFS, and OS were 76%, 64%, and 69%, respectively. Of 24 irradiated lesions in CR in at day+30, 2 (8%) progressed locally; however, of 8 irradiated lesions in PR at day+30, 5 (63%) progressed locally. One lesion had local progression at day+30. PR at day+30 was associated with worse LC (p=0.003), PFS (p=0.02), and OS (p=0.01). Most treated sites were nodal (76%), mainly in the abdomen and pelvis. No local failures were seen in irradiated extranodal bone or soft tissue sites. LC was not associated with receipt of systemic bridging therapy (p=0.69), radiation dose (p=0.92), tumor size (p=0.10), or SUV (p=0.20). Thirteen patients experienced grade 2 CRS, and one instance each of grade 3 and 4 CRS. One and three patients had grade 2 and 3 ICANS. Median LDH before and after BRT was 422 and 219 U/L. Higher pre-BRT LDH was associated with worse LC (p=0.016) and PFS (p=0.002). Patients with a normal LDH (<250 U/L) prior to BRT had no local or distant failures. Patients for whom LDH normalized after BRT were less likely to progress overall (p=0.041).Conclusion: BRT offers excellent LC with low rates of CRS or neurologic toxicity for patients with bulky tumors undergoing CAR-T. Patients with a suboptimal MTV or LDH response after BRT may benefit from adaptive dose intensification or combined modality approaches. Patients with suboptimal response at day+30 (e.g. PR), should be considered for early intervention, including additional radiotherapy, bispecific antibody therapy, or hematopoietic cell transplantation.