Analysis of Metabolic Tumor Volume in Patients Undergoing Bridging Radiotherapy Prior to CAR-T Therapy for Relapsed/Refractory Aggressive B Cell Lymphoma

Purpose/Objective(s)

High baseline metabolic tumor volume (MTV) is associated with decreased progression-free and overall survival in patients with aggressive relapsed/refractory B-cell lymphoma (R/R BCL) undergoing CAR-T therapy. Bridging radiation therapy prior to CAR-T infusion is safe and may be an effective tool in cytoreduction. However, appropriate target delineation and the impact of bridging radiotherapy on CAR-T therapy outcomes remain undefined. This study analyzed baseline MTV characteristics and post-CAR-T outcomes in a cohort of patients undergoing bridging radiation therapy prior to CAR-T therapy for R/R BCL.

Materials/Methods

We performed an IRB-approved retrospective cohort study including patients with R/R BCL who underwent bridging radiation therapy prior to CAR-T infusion at a single institution from 10/2017 to 01/2022. We measured baseline patient and bridging radiation treatment characteristics along with baseline disease burden as defined by MTV. MTV calculations were made using commercially available software. The primary outcome was metabolic response on 28-day post-CAR-T positron emission tomography (PET) imaging.

Results

We identified 10 patients who completed bridging radiation therapy; 8 completed CAR-T apheresis and infusion, 1 completed CAR-T apheresis with infusion pending, and 1 is pending CAR-T apheresis and infusion. Seven of 9 patients initiated bridging radiation treatment after CAR-T apheresis (median 3 days after). The median time between the completion of bridging radiation treatment and CAR-T infusion was 11.5 days (range: 5-28 days). Bulky disease (>7.5 cm) and elevated LDH were present in 70% and 100% of patients, respectively. Median baseline total MTV was 244.2 mL (range: 11.4-805.0 mL), median irradiated MTV was 152.8 mL (range: 11.4-802.6 mL), and the median proportion of MTV that was irradiated was 97% (range: 9%-100%); 9 of 10 patients underwent radiation to 75% or greater of the total MTV. Post-CAR-T 28-day PET imaging (available for N = 6 patients) demonstrated a partial metabolic response for 3 patients and complete metabolic response for 2 patients; 1 patient had disease progression at 28-day PET. The complete metabolic response rate of irradiated areas was 67% at 28-day post-CAR-T PET and 100% on subsequent PET imaging. Radiation-related side effects were minimal: 6 of 10 patients experienced Grade 1 toxicity which resolved and 4 of 10 patients experienced no side effects.

Conclusion

Although the number of patients is small, we found that patients with high-risk R/R BCL, including those with high MTV, were successfully treated with bridging radiation therapy that encompassed a large percentage of their disease (median 97%) prior to CAR-T infusion and achieved encouraging post-CAR-T PET responses with minimal toxicity.