201 - Treatment Kinetics and Local Response during and after Bridging Radiotherapy prior to CAR-T Cell Therapy for Lymphomas
Presenter(s)
D. Klebaner1, N. J. Park1, M. Marar1, M. Frank2, S. M. Hiniker1, R. T. Hoppe1, J. Schroers-Martin3, R. H. Advani3, A. A. Alizadeh3, S. Bharawadj2, D. Miklos2, S. Dahiya2, and M. S. Binkley1; 1Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 2Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, 3Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA
Purpose/Objective(s): Bridging radiotherapy (BR) prior to CAR-T for non-Hodgkin lymphoma (NHL) provides effective cytoreduction, but optimal dosing to balance efficacy and toxicity remains undefined. We evaluated 33 patients with relapsed/refractory NHL who received BR and CAR-T at our institution (2019-2024) with post-treatment PET/CT. We assessed the role of real-time radiotherapy response and clinicopathologic features in local control. Based on our findings, we initiated a protocol for a personalized and adaptive BR approach.
Materials/Methods: In the retrospective phase, we evaluated radiation response by contouring gross tumor volume (GTV) on cone beam CT (CBCT) from the first 5 fractions, and used a cutpoint analysis to identify a threshold for “rapid bridging response” (RBR). We estimated 18-month cumulative incidence of local progression with death as a competing risk. Gray’s test was used to compare the cumulative incidence of local progression by histology, RBR status, pre-treatment LDH, MTV, and age. Significance level was alpha=0.1. The prospective protocol incorporates dose personalization based on pre-specified clinicopathologic features, and adaptive dose reduction with early truncation of radiotherapy after 4 of 5 or 6 of 10 fractions for patients with RBR. Patients with MCL, disseminated DLBCL, or bowel involvement are prescribed lower dose regimens (24 Gy/10 fractions or 20.5 Gy/5 fractions), while those with localized or bulky disease or local metabolic tumor volume (MTV) >100 cc are prescribed higher doses (33 Gy/10 fractions or 27.5 Gy/5 fractions).
Results: The retrospective cohort consisted of 23 patients with diffuse large B-cell lymphoma (DLBCL), 8 with mantle cell lymphoma (MCL), and 2 with primary mediastinal B-cell lymphoma. Post-CAR-T, 28/33 patients experienced a complete response (CR) as their best response at the irradiated site, and 5 experienced a partial response (PR). Nine of 25 patients with available CBCT experienced RBR, defined as =10% volume shrinkage within 5 radiation fractions, and 6/33 patients had local progression (18-month cumulative incidence 19% [95% CI 7.5-35]), none of whom had RBR. There was not a notable difference in sex, chemo-refractory disease, or radiotherapy EQD2 between patients with and without local progression. Factors associated with a higher cumulative incidence of local progression included the absence of RBR, LDH=375 U/L, and MTV =100 mL (all p<0.1), while there was a trend toward lower local progression with age>60 years and MCL histology, with no local recurrences among MCL patients. Since August 2024, the prospective protocol has completed pre-planned initial enrollment of 10 patients, 4 of whom exhibited RBR.
Conclusion: Clinicopathologic and radiomic features, as well as real-time radiotherapy response, may guide a personalized and adaptive approach to BR. Preliminary analysis of outcomes from our prospective protocol are anticipated by mid-2025.