Bridging radiotherapy to CAR-T cell therapy in refractory non- Hodgkin B lymphoma: Singlecenter experience

ABSTRACT

Background: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is an effective option for the treatment of relapsed/refractory diffuse large B-cell lymphoma. In order to control lymphoma progression during the manufacturing period, a bridge therapy regimen is required for most patients. Radiotherapy (RT) may be used for patients with localized chemorefractory disease as a bridge therapy. Patients Here we report a case series of 6 patients (1 primary mediastinal, PMBCL, and 5 diffuse large B-cell lymphoma, DLBCL) treated with radiotherapy as bridge to CAR-T. (Figure 1 summarizes the treatment history). Four patients received tisagenlecleucel (tisa-cel), and one axicabtagene- ciloleucel (axi-cel);one patient died before reinfusion of CAR-T. Results: The dose of RT was 30 Gy in 15 fractions, the site was mediastinum for pt 001, abdominal adenopathy for pt 002, 003 and 005, inguinal adenopathy for pt 004, laterocervical adenopathy for pt 006). Median volume of irradiation was 210 ml (avg. 270 ml, min 79,6 ml, max 635 ml). Response to bridging RT was achieved in 3/ patients (2 PR, 1 CR), one patient had stable disease, and one patient ha disease progression at the time of CAR-T infusion. One patient died for severe Covid19 pneumonia before receiving the planned CART infusion. The outcome is favorable at the time of writing for all infused patient but one, who died for progression 3 months after infusion (the one with progressive disease at the time of infusion). Toxicity was manageable, with no grade 3-4 CRS;maximum CRS grade was 2 in 3 cases. Only one patient receiving axi-cel needed admission at ICU for grade 4 ICANS, with complete resolution after treatment with high dose steroids. Conclusions: We showed in this report that RT is feasible and effective as bridging therapy for patients with localized disease before CAR-T therapy.