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Is Bridging Radiation (RT) Safe with B Cell Maturation Antigen–targeting Chimeric Antigenic Receptor T Cells (CART-BCMA) Therapy?

      Purpose/Objective(s)

      Our institution conducted a phase I study to evaluate CART-BCMA in patients with relapsed/refractory multiple myeloma (MM). We hypothesized that bridging RT, defined as RT delivered after apheresis but before CART infusion, was a safe and feasible approach in MM.

      Materials/Methods

      25 MM subjects were treated in 3 cohorts: 1) 1-5 x 108 CART-BCMA cells (n = 9); 2) Cyclophosphamide (Cy) 1.5 g/m2 + 1-5 x 107 CART-BCMA cells (n = 5); and 3) Cy 1.5 g/m2 + 1-5 x 108 CART-BCMA cells (n = 11). Protocol methods have been published. We retrospectively collected details on RT, response, toxicity, and CART manufacturing data. Toxicity was graded per CTCAE version 4.0 and cytokine release syndrome (CRS) per institutional CRS Grading System. Responses were scored by the updated IMWG criteria.

      Results

      13 subjects received no RT within 1 year prior to CART infusion (Group 1). 8 subjects received RT within 1 year prior to CART infusion (Group 2) with median time from RT to apheresis of 88.5 days (range 15-295). 4 subjects received bridging RT (Group 3) with a median time from apheresis to RT of 17 days (14-22) and from RT to CART infusion of 34 days (21-42). RT sites in Group 3 included skull base, spine, pelvis, and orbits; treated with 4 Gy x 5 fractions, 8 Gy x 1, 4 Gy x 6, and 3 Gy x 10 using 3D-conformal RT. Group 3 had lower rates of grade (G) 4 hematologic toxicities vs. 1 and 2 (25% vs. 61.5% and 62.5%). Group 3 also had no ≥G3 gastrointestinal, infectious, or liver-related toxicities. Neurotoxicity was low with G3 toxicities at 7.7%, 25%, and 25% in the Group 1, 2, and 3 respectively and two G4 toxicities observed in Group 2 only (25%). G2 CRS was comparable among the groups while G3 CRS was slightly higher in Group 1 (38.5% vs. 25% in Group 2 and 3). Only Group 2 had one G4 CRS (12.5%). Response rates are shown in Table 1. Prior analysis revealed a lower dose of CART-BCMA cells led to the smallest response so we compared cohort 2 patients with and without bridging RT. Cohort 2 patients without bridging RT (n = 3) had no response whereas those with bridging RT (n = 2) had MR and PR both in and out of the RT field.

      Conclusion

      Our results suggest that bridging RT is safe and feasible without worsening rates of severe CRS, neurotoxicity, or hematologic toxicity. Future prospective trials combining RT with CART-BCMA may further optimize safety and long-term efficacy of this novel therapy in relapsed/refractory MM.
      Abstract 1104; Table 1Rates of best response in Group 1, 2 and 3. CR = complete response, VGPR = very good partial response, PR = partial response, MR = minimal response, SD = stable disease, PD = progressive disease. Manufacturing of CART-BCMA cells was successful across all groups with comparable rates of expansion, transduction efficiency, and day of peak cells in vivo.
      GroupCR (%)VGPR (%)PR (%)MR (%)SD (%)PD (%)
      1 (n = 13)15.323.115.315.330.80
      2 (n = 8)02512.512.52525
      3 (n = 4)00505000

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