Durable responses to 3rd party viral specific T cells mediated by different patterns of engraftment

Background & Aim Background Adoptive therapy with 3rd party virus-specific T cells has demonstrated efficacy in the treatment of refractory infection complicating hematopoietic stem cell (HCT) and solid organ (SOT) transplant. A striking feature of responses observed at our center has been their durability. We have previously demonstrated that expansion of the infused viral specific T cells lasting for 3-6 wks is observed in patients (pts) responding to transplant donor-derived or 3rd party T cells. The durability of response to HCT donor-derived T cells is expected; however, the durability of response to 3rd party T cells, which are expected to be rejected, is unexplained. Methods, Results & Conclusion Methods We have evaluated pts responding to 3rd party EBV-specific T cells (tabelecleucel) and CMV CTLs for the durability of response through 12-mo and whether the durability of response correlates with overall survival (OS) and depends on persistence of 3rd party viral specific T cells. We evaluated HCT pts treated for CMV viremia and/or disease who responded to 3rd party CMV-CTLs (N=32) and HCT and SOT pts with rituximab refractory EBV+ PTLD who responded to tabelecleucel (N=29). To detect in vivo persistence of 3rd party T cells we sorted viral specific T cells and performed analysis by short tandem repeats (STRs). This method is especially well suited to detection of even rare CMV specific T cells where the epitope recognized by the infused population has been defined. Results Clinical responses were durable at 1 year in 57/61 pts. This durability correlated to improved OS. Pts responding to CMV-CTL therapy had 12-mo OS of 80.3%. In contrast 12-mo OS for pts not responding to CMV CTLs was 33.3%. Pts responding to tabelecleucel had 12-mo OS of 93.1%. with 12-mo OS of 12.5% in non-responders. We demonstrated three patterns of persistence of CMV-CTLs in HCT pts ranging from very transient detection up to detection for 9 mos after infusion. Conclusion Our studies provide evidence that, while initial response can be ascribed to the function and expansion of the T cells administered, the durability of response in HCT pts does not depend on detectable 3rd party cells.