Bridging RT Before CAR T-Cell Therapy Can Benefit Patients With R/R DLBCL

Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) may benefit from bridging radiation therapy (bRT) ahead of receiving chimeric antigen receptor (CAR) T-cell therapy, according to an abstract presented at the 2023 American Society for Radiation Oncology (ASTRO) Annual Meeting and published in the International Journal of Radiation Oncology, Biology, Physics.¹

Lymphoma | Image credit: Dr_Microbe - stock.adobe.com

DLBCL is an aggressive form of non–Hodgkin lymphoma (NHL), and bridging therapy may be needed to control a patient’s disease before CAR T-cell therapy. While treatment with CAR T cells has shown favorable results in patients with R/R DLBCL, growing demand for these therapies has led to delays in eligible patients receiving them.²

The study authors aimed to determine whether there are patient characteristics or treatment factors associated with outcomes following bRT and CAR T-cell therapy among patients who received axicabtagene ciloleucel (axi-cel; Yescarta) between November 2017 and December 2022. Axi-cel is a CD19-targeted autologous CAR T-cell therapy approved for the treatment of patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that has relapsed within 12 months of first-line chemoimmunotherapy.³

A total of 40 patients with DLBCL who received bRT before axi-cel infusion were included in the retrospective study. Researchers gathered data on clinical and treatment characteristics, responses to therapy, and toxicity, and modeled progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) using Kaplan-Meier estimates.

Of the 40 patients, 11 (28%) had limited stage disease at the time of apheresis to collect CAR T cells. A total of 14 patients (35%) received bRT and systemic bridging therapy, and 32 (80%) patients received bRT after leukapheresis. The median dose of radiation therapy was 30 Gy (range, 4-26) in 10 fractions (range, 2-23), and 18 patients (45%) received less than 30 Gy. Additionally, 22 patients (55%) received bRT comprehensively at all disease sites, 9 of whom had limited stage disease. At the time of bRT, bulky disease (≥ 10 cm) was noted in 11 patients.

A total of 23 patients (57.5%) experienced complete response (CR) to CAR T-cell therapy at 30 days post-treatment, 9 patients (22.5%) experienced a partial response (PR). Two of the patients who had PRs experienced CR by 3 months post-infusion, and 1 CR occurred at 9 months. Following CAR T infusion, grade 3 or higher cytokine release syndrome (CRS) occurred in 4 patients (10%), while 16 patients (40%) showed grade 2 or higher CRS, and grade 3 or higher neurotoxicity occurred in 16 patients (38%).

Eleven of the patients who had CRs relapsed, with 6 relapsing at 3 months and 5 at 6 months post treatment. Overall, 22 patients had relapsed at a median follow-up of 9.6 months (95% CI, 6.6-16.2). The overall median PFS was 8.87 months, and the median OS was 22 months. At 1 and 2 years, PFS was 70% and 42%, respectively. As for OS, the rates at 1 and 2 years were 72.5% and 51%, respectively.

Univariate analysis found that among patients who received comprehensive RT, OS was 67% and PFS was 49% at 1 year. In patients who did not receive RT comprehensively, OS was 41.9% and PFS was 33.3% at 1 year (P ≤ .03). While there was a significant association between bulky disease and worse DSS (P = .03), disease bulk and PFS or OS were not significantly associated. Disease bulk was not associated with OS, PFS, or DSS in patients who received comprehensive bRT. There were also no significant PFS, OS, or DSS differences in patients who underwent bRT alone vs systemic therapy and RT.

“bRT and [CAR T-cell therapy] is a good treatment strategy for select patients with aggressive B-cell lymphoma,” the authors concluded. “When feasible, and with a caveat that other variables influence patient disposition, bRT for CAR T is associated with improved outcomes after comprehensive RT to all sites of disease."

References

1. Manzar GS, Wu SY, Dudzinski SO, et al. Outcomes with bridging radiation therapy prior to CAR-T cell therapy in pts with aggressive B cell lymphomas. Int J Radiat Oncol Bol Phys. 2023;117(2):e483-e484.doi:j.ijrobp.2023.06.1708

2. Tomtishen J. The role of automation in meeting the growing demand for CAR T-cell therapies. Am J Manag Care. 2023;29(5 Spec No.):SP427-SP428. doi:10.37765/ajmc.2023.89391

3. Yescarta (axicabtagene ciloleucel). Prescribing information. Kite Pharma;2022. Accessed October 5, 2023. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/yescarta-axicabtagene-ciloleucel