Prevalence of Non-Hodgkin Lymphoma Patients at High Risk of Failure after CAR T-Cell Therapy Eligible for Bridging Radiation Therapy.

Abstract

CD19-directed chimeric antigen receptor T-cell therapy (CART) has led to remarkable outcomes in patients with relapsed or refractory (R/R) non-Hodgkin's lymphomas (NHL), yet ∼50% of patients relapse. Predictive factors associated with high risk of relapse following CART have been identified in the literature. Studies have shown a potential improvement in outcomes with the use of bridging radiation (RT) prior to CART. The purpose of this study is to determine the incidence of patients meeting high risk criteria who have disease that could be encompassed in a standard radiation plan prior to CART. This was a single-center, retrospective study of patients with R/R NHL who received CART from 2018 to 2022. Data were obtained from the EHR and manual chart review was used to identify patients with disease encompassable in a standard radiation plan defined as <5 malignant lesions on pre-apheresis radiological studies. These patients were then screened for presence of ≥1 high risk criteria: bulky disease ≥10 cm, ≥1 extranodal (EN) sites, LDH ≥normal, or ≥1 lesion with SUVmax ≥10. Descriptive statistics were used to make inferences about the population. Eighty-one R/R NHL patients were evaluated with a median age of 65 years (range 23-84), 60% male, and received a median of 2 (range 1-7) prior lines of therapy. CART products included axi-cel (62%), brexu-cel (7%), liso-cel (16%), and tisa-cel (15%). Forty (49%) patients would have been eligible for bridging RT (<5 sites on pre-apheresis radiologic studies), including 29 patients who met high risk criteria: 19 had ≥1 lesion with SUVmax ≥10, 16 with bulky disease, 6 with ≥1 EN site, and 3 with elevated LDH. At 3 months post-CART, clinical response data were available for 19 high risk patients with ORR of 79% (11 CR, 4 PR, 1 SD, and 3 PD), compared to 8 patients with standard risk disease with ORR of 88% (7 CR and 1 PD). Of those with less than a CR, 8/9 met high risk criteria: 4 with bulky disease, 6 had ≥1 lesion with SUVmax ≥10, and 2 with ≥1 EN site. There were 9/40 patients who received bridging therapy, and only 2 high risk patients received bridging RT. One patient with transformed DLBCL had persistent disease in the nasopharynx following RCHOP x3C and R-HyperCVAD, and received 20 Gy/10 fx as a bridge to CART resulting in a continued CR at 23 months of follow-up. Another patient with non-DH, GCB-like DLBCL received R-CHOP x6C (achieved CR) but relapsed <1 year later and then received R-ICE x2C with PD in the left shoulder, which was radiated with 30 Gy/10 fx for pain as a bridge to CART, but experienced disease relapse 6 months after CART. Approximately 35% (28/81) of patients were classified as high risk of relapse after CART and had disease encompassable in a standard radiation plan. Of these patients, 44% (8/18) experienced either PR, SD or PD at 3 months post-CART. Future studies are needed to determine the role of bridging RT prior to CART as a strategy to improve outcomes and prevent relapse in high-risk NHL patients.