Investigating Metabolic Response after CAR-T Therapy and Bridging Radiotherapy for Relapsed/Refractory B-Cell Lymphoma

Introduction: For patients with aggressive relapsed/refractory B-cell lymphoma (R/R BCL) undergoing CAR-T therapy, metabolic treatment response assessed at the 1-month interval following CAR-T infusion is associated with likelihood of disease progression (Kuhnl A, et al. Blood Adv 2022). In particular, SUV max on 1-month ¹⁸F-FDG positron emission tomography (PET) imaging is predictive of disease progression (Zaki A, et al. Blood Adv 2022). However, for patients who undergo bridging radiotherapy (RT) prior to CAR-T infusion, it remains unclear how to interpret metabolic activity for irradiated sites on surveillance PET imaging following CAR-T. We sought to characterize metabolic activity after CAR-T and bridging RT in a cohort of patients with R/R BCL.

Methods: This IRB-approved retrospective cohort study included patients with R/R BCL who underwent bridging RT prior to CAR-T infusion at a single institution from January 1, 2019 to April 30, 2022. We measured baseline patient characteristics, treatment factors, and PET metrics prior to bridging RT. We then assessed tumor metabolic activity on surveillance PET imaging following CAR-T infusion until the time of disease progression (defined as Deauville 5 disease) or last follow up.

Results: We identified 10 patients who completed bridging RT prior to CAR-T infusion with at least one post-CAR-T disease assessment with PET imaging. Median follow up was 152 days from CAR-T infusion (range: 31-1095). Most patients (90%) had bulky disease (≥7.5 cm) and all had elevated LDH at baseline. Bridging RT dosing ranged from 20-38.5 Gy (median: 20 Gy) over 5-14 fractions (median: 5 fractions). Bridging RT fields were directed at bulky disease sites for 8 of 9 patients with bulky disease. The median metabolic tumor volume (MTV) irradiated with bridging RT was 149 mL (range: 26-803) and the median proportion of total MTV irradiated was 97% (range: 8.7-100). The median time between pre-bridging RT PET imaging and CAR-T infusion was 49 days (range: 37-124) and the median time between the end of bridging RT and CAR-T infusion was 12 days (range: 5-106). On pre-bridging RT PET, the median SUV max in the irradiated field was 23.3 (range: 9.1-36.1) (Figure 1). On 1-month post-CAR-T PET, the median SUV max in the irradiated field decreased to 3.2 (range: 0-6.1) and median delta SUV max was -87% (range: -68% to -100%). At the 1-month post-CAR-T interval, 40% of patients had a complete metabolic response (Deauville 3 or below), 40% had Deauville 4 disease, and 20% had Deauville 5 disease. Among the 4 patients with Deauville 4 disease at 1-month post-CAR-T, 3 patients developed complete metabolic responses and 1 patient had persistent Deauville 4 disease on subsequent PET imaging. No patients in the cohort developed disease progression within the irradiated fields. At last follow up, 3 patients had developed Deauville 5 disease, and for 2 of the 3 patients, areas of disease progression included unirradiated sites of disease that were present on pre-bridging RT PET imaging.

Conclusions: In this small retrospective cohort of patients undergoing bridging RT prior to CAR-T therapy for R/R BCL, patients with concern for refractory disease on initial imaging assessment demonstrated complete response or stable disease on subsequent follow up imaging. Caution may be warranted in interpreting metabolic activity levels on initial post-CAR-T surveillance PET imaging, and validation in larger cohorts is needed to better understand metabolic activity dynamics in disease sites treated with bridging RT prior to CAR-T therapy.

Figure 1. SUV Max in Disease Sites Treated with Bridging RT*

*Each line corresponds to one patient treated with bridging RT prior to CAR-T therapy. SUV max plotted on the vertical axis reflects metabolic activity within the irradiated fields. Time intervals indicated in months on the horizontal axis reflect the approximate time from CAR-T infusion with the exact range in days indicated in parentheses. The magnification box demonstrates metabolic activity at the 1-month post-CAR-T interval with corresponding Deauville score indicated by color.

Marar:Bristol Myers Squibb: Consultancy.