Feasibility and outcome of bridging RT pre CAR-T in DLBCL in one centre with a wide referral network

ABSTRACT

Purpose or Objective CD19 CAR-T therapy is the most effective salvage treatment for relapsed/refractory DLBCL. However the manufacture of CAR-T cells takes several weeks and patients (pts) are at risk of progression during this time and usually require some form of bridging therapy to contain their disease. Radiotherapy (RT) is an attractive bridging option, as the chance of response to further conventional cytotoxic therapy is low. RT is generally delivered in the window between apheresis and infusion and requires careful scheduling. The aim of this study is to evaluate the feasibility, toxicity and early outcome of bridging RT in a cohort of pts undergoing CAR-T therapy for DLBCL. Materials and Methods This was a prospective analysis of pts receiving bridging RT since the start of CAR-T programme at our institution. We collected data on pt demographics, disease and RT details, as well as outcomes including early response, relapse, survival and toxicity. Results (Table presented.) Between April 2019 & January 2021 a total of 27 pts have received bridging RT. Of these 23 have been infused (1 not infused due to COVID19, 1 due to cardiac function & 2 pending). The CAR-T therapy was delivered in 1 Haematology Institution, but bridging RT in 9 different referring centres. Pt and disease characteristics and RT details are shown in table 1. The median time from CT planning scan to start of RT was 10 days (4-42). The median time between apheresis and start of RT was 5 days (-37-21;3 patients received RT prior to apheresis at -37,-35 &-29 days) and median time between end of RT and CAR-T infusion was 19 days (10-116). No pts were delayed due to RT toxicity. Toxicity data was available for 22 pts. 10 (45.5%) reported no toxicity. Only 1 pt had grade 3 toxicity (vomiting & diarrhoea) and RT was stopped. The most common toxicities were skin reaction (n=5) & fatigue (n=4). 25/27 (92.6%) pts underwent a PET-CT between bridging RT & infusion. In 22 (88%) pts there was response in treatment field (CMR=2, PMR=20). In 13 (59.1%) of those pts there was evidence of progressive disease (PD) outside the field, but none were prevented from receiving CAR-T infusion due to PD. With median FU of 8.8 (0.6-20.6) months from date of CAR-T infusion, 12/ 23 (52.2%) infused pts have relapsed, (2 infield, 5 out of field, 5 in both) with a local control rate of 69.6%;CMR (12;52.2%) and PMR (4;17.4%). 7 pts have died since infusion, 6 due to PD and 1 due to sepsis. Median PFS was 5.1 months (95% CI 0.0-11.9 months) and median OS 17.8 months (95% CI 12.7-22.9 months). 1 pt had infusion delayed due to COVID19 infection and died of PD. Conclusion RT was a safe and effective bridging option in this cohort of DLBCL pts pre CAR-T therapy. With close collaboration between Haematologists and Radiation Oncologists, it is possible to deliver a course of radical dose RT in the narrow window between apheresis and infusion, even across a wide geographical network. Further work is required to determine which pts benefit most from bridging RT and the optimal dose and schedule.