Bridging and Salvage Radiotherapy Significantly Improved In-Field Control Among Patients With R/R MCL

Findings from a retrospective study published in the International Journal of Radiation Oncology indicated that the use of radiotherapy (RT) as a bridging and salvage approach significantly improved in-field control outcomes and limited toxicity among patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) undergoing CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. 

Dr H Ababneh, Massachusetts General Hospital, Boston, Massachusetts, and coauthors aimed to provide insight on their “early experience of using bridging and salvage radiation therapy (RT) in patients with relapsed/refractory mantle cell lymphoma (MCL) undergoing CD19-targeted chimeric antigen receptor (CAR) T-cell therapy.” 

A total of 21 patients with MCL who had received CD19-targeted CAR T-cell therapy between 2020 and 2022 were enrolled in this study. These patients consisted of 17 who had received brexucabtagene autoleucel, 3 who had received tisagenlecleucel, and 1 who had received lisocabtagene maraleucel. Patients who had received RT prior to and after CAR T-cell therapy were determined and examined using descriptive and statistical analysis. 

Using the Kaplan-Meier method, the overall survival from the date of CAR T-cell infusion was estimated. The study authors defined the duration of local control (LC) as the time between the start date of RT and the date of in-field progression/relapse. Response to RT was interpreted based on the total number of irradiated sites. 

Results demonstrated that the median overall survival was 17 months (95% confidence interval [CI], 14.2 months to not reached). Among the patients, 1 received bridging RT before CAR T-cell infusion, 1 received RT before and after CAR T-cell infusion, and 5 received salvage RT after CAR T-cell infusion, with a total of 23 irradiated sites. Sites of RT consisted of extremities (10), central nervous system (3), pelvis/groin (3), head and neck (3), chest (2), abdomen (1), and multiple sites (1). The median dose/fractionation was 16.5 Gray (Gy) (ranging from 3.6 to 45 Gy) and 5.5 fractions (ranging from 2 to 16 fractions). Among the patients, 1 had incomplete radiation data. 

Among the 21 evaluable sites, 86% reached complete response (n = 18) and 14% reached partial response (n = 3), which translates to an LC rate of 100%. There were 2 inevaluable sites due to patient mortality after receiving RT due to progressive lymphoma. Of the 9 sites receiving low-dose RT, 67% (n = 6) reached complete response and 33% (n = 3) reached partial response, indicating that there was no correlation between RT dose and LC. In terms of safety, 1 patient had grade 3 to 4 RT-related toxicities. Additionally, at the time of the final follow-up, 4 patients remained alive, and 3 patients experienced progressive lymphoma. 

Using low-dose radiotherapy yielded similar results to high doses, indicating that RT dose and LC were uncorrelated. Dr Ababneh et al concluded that, “our early experience underlines that using RT as a bridging and salvage approach is associated with excellent in-field control and limited toxicity in the peri-CAR T setting. Low-dose RT for MCL appears to be very effective in this highly refractory population and warrants further investigation.”

“No studies exclusively focusing on CAR T-cell therapy and bridging or salvage RT have been published among relapsed/refractory MCL patients,” they added. 

Source: 

Ababneh H, Frigault M, Patel CG. Outcomes of bridging and salvage radiotherapy in relapsed or refractory mantle cell lymphoma patients undergoing CD19-targeted CAR T-cell therapy. Int J of Rad Oncol. Published online: October 1, 2023. doi: 10.1016/j.ijrobp.2023.06.1646