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Bridging Radiotherapy before CAR-T for High Grade Lymphoma – Feasibility & Efficacy

      Purpose/Objective(s)

      CD19 CART is the most effective salvage in chemo-refractory high-grade NHL. Preparation of engineered T-cells takes 4 weeks and the average duration from approval to infusion is 6-8 weeks, during which the disease may progress. Radiotherapy (RT) can be used as a bridging therapy to holt disease progression and stabilize patient performance status & organ function to enable CART. The purpose of this study is to evaluate whether it is feasible to deliver bridging RT within the tight CART schedule, its success in enabling CART and its additional toxicity. Our hypothesis is that bridging RT is feasible in symptomatic & progressive disease and is effective in enabling successful CAR-T without increasing toxicity.

      Materials/Methods

      We reviewed all patients (pts) treated in our institution since CART therapy became routinely available. Data is prospectively collected. We identified pts who were considered for bridging RT and reviewed their treatment details & disease course.

      Results

      Since January 2019, 54 pts received CART in our institution. Bridging RT was considered in 15 pts; 9 treated in our institution and 6 in referring institutions. Median age of 9 pts was 62 years (19-72) & 5 were males. 8 pts completed RT & received CART successfully. 1 patient with large abdominal mass had RT planning completed but developed intestinal perforation on D1 before starting & died without treatment. RT indications were local and symptom control in 8 pts and local control only (sanctuary site) in 1. Table 1 shows details of RT and CART treatments. RT was given after apheresis in 7 pts, before apheresis in 1 and as a split course before & after apheresis in 1, always allowing 2 weeks window from RT to apheresis. The median time from first appointment to starting RT was 11 days (0-22) and from simulation/planning to starting RT was 8 days (0-21). The median time from simulation to plan approval is 4 days (0-6) for all patients & 5 days (2-6) for VMAT. There was no grade ≥3 acute toxicity from RT & no unplanned delays in CART infusion due to RT. The median apheresis-RT time was 5 days (-36 – 26) and from apheresis-infusion was 40 days (34 – 57). Post-CAR-T toxicity & 3 months response are shown in Table 1.

      Conclusion

      Bridging RT is feasible in the majority of patients with predominantly locally progressive disease and is effective in slowing disease progression & stabilizing patients until CART infusion. Close cooperation between Hematologists & radiation oncologists is essential for timely delivery of treatment. RT is well tolerated & toxicity after CART does not seem to have increased.
      Abstract 1105; Table
      Histological type DLBCL (transformed) PMBCLNo 6 2 1
      CART product Axicel TisagenNo 7 2
      RT site Neck Abdomen Spine Chest wall Mediastinum ScrotumNo 2 2 2 1 1 1
      Dose 36Gy/18# 35Gy/15# 30Gy/15# 24Gy/12# 20Gy/5# 8Gy/2#No 1 1 4 1 1 1
      Technique VMAT Simple electronsNo 6 2 1
      CAR-T toxicity - G 0 G 1 G 2 G 3 G 4CRS RT 2 1 4 1 0CRS No RT pts (n = 40) 2 16 18 4 0ICANS RT 6 1 0 0 1ICANS No RT pts (n = 40) 28 4 2 4 2
      Response (3 months) CMR PR PD DeathNo 2 2 3 2 (1 PD + 1 sepsis)

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