Rossig, C; Pule, M; Altvater, B; Saiagh, S; Wright, G; Ghorashian, S; Clifton-Hadley, L; ... Amrolia, PJ; + view all Rossig, C; Pule, M; Altvater, B; Saiagh, S; Wright, G; Ghorashian, S; Clifton-Hadley, L; Champion, K; Sattar, Z; Popova, B; Hackshaw, A; Smith, P; Roberts, T; Biagi, E; Dreno, B; Rousseau, R; Kailayangiri, S; Ahlmann, M; Hough, R; Kremens, B; Sauer, MG; Veys, P; Goulden, N; Cummins, M; Amrolia, PJ; - view fewer (2017) Vaccination to improve the persistence of CD19CAR gene-modified T cells in relapsed pediatric acute lymphoblastic leukemia. Leukemia , 31 pp. 1087-1095. 10.1038/leu.2017.39.

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Abstract

Trials with 2nd generation CD19 chimeric antigen receptors (CAR) T-cells report unprecedented responses but associated with risk of Cytokine Release Syndrome (CRS). Instead, we studied use of donor Epstein Barr virus-specific T-cells (EBV CTL) transduced with a 1st generation CD19CAR, relying on the endogenous T-cell receptor for proliferation. We conducted a multi- center phase I/II study of donor CD19CAR transduced EBV CTL in pediatric ALL. Patients were eligible pre-emptively if they developed molecular relapse (>5 × 10-4) post-1st SCT, or prophylactically post-2nd SCT. An initial cohort showed poor expansion/persistence. We next investigated EBV-directed vaccination to enhance expansion/persistence. 11 patients were treated. No CRS, neurotoxicity or GVHD was observed. At 1 month, 5 patients were in CR (4 continuing, 1 de-novo), 1 PR, 3 had stable disease and 3 no response. At a median follow-up of 12 months, 10 of 11 have relapsed, 2 are alive with disease and 1 alive in CR 3 years. Whilst CD19CAR CTL expansion was poor, persistence was enhanced by vaccination. Median persistence was 0 (range 0-28) days without vaccination compared to 56 (range 0-221) days with vaccination (P=0.06). This study demonstrates feasibility of such multi-center studies and the potential for enhancing persistence with vaccination.Leukemia accepted article preview online, 27 January 2017. doi:10.1038/leu.2017.39.

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