Despite the increased usage of post-transplant cyclophosphamide (PTCy) in allogeneic hematopoietic stem cell transplantation (allo-HSCT), our knowledge of immune reconstitution post-allo-HSCT in the setting of PTCy is limited. Adequate immune reconstitution is the key to a successful transplant. In this study, we aim to investigate the effect of PTCy on the reconstitution of each immune component; more focus was placed on the immunophenotype and functions of T cells. Using blood samples from patients who underwent allo-HSCT under regimens containing PTCy (n = 23) versus those who received no PTCy (n = 14), we examined the impact of PTCy on the post-transplant immune response. We demonstrated a distinct T cell immune signature between PTCy versus non-PTCy group. PTCy significantly delayed T cell reconstitution and affected the T cell subsets by increasing regulatory T cells (Treg) while reducing naïve T cells. In addition, we observed remarkable enhancement of multiple inhibitory receptors (TIGIT, PD-1, TIM-3, CD38, CD39) on both CD4+ and CD8+ T cells on day 30 post-transplantation in patients who received PTCy. Importantly, upregulation of PD-1 on CD8 T cells was persistent through day 180 and these T cells were less functional, manifested by reduced cytokine production upon anti-CD3/CD28 stimulation. Furthermore, we found a significant correlation of T cell immune phenotypes to clinical outcome (disease relapse and GVHD) in patients who received PTCy. Our novel findings provide critical information to understand the mechanism of how PTCy impacts immune reconstitution in allo-HSCT and may subsequently lead to optimization of our clinical practice using this treatment.

e17565 Background: We previously reported the significant prognostic and predictive utility of pretreatment serum PD-L1 in the CCTG MA.31 breast cancer serum bank (SABCS 2018, abstr PD3-10). IL-8 (CXCL8) is a pro-inflammatory cytokine that binds to CXCR1 and CXCR2 and promotes tumor immune escape and progression. High serum IL-8 levels are associated with poor prognosis in many cancers, and have recently been reported to predict for reduced overall survival (OS) to nivolumab in lung cancer and melanoma (ASCO 2018, abstr #3025). Here we correlated plasma IL-8 and PD-L1 levels with OS in mCRPC patients. Methods: 201 metastatic CRPC patients had EDTA plasma available for this retrospective analysis. Patient eligibility included chemotherapy-naive mCRPC patients. The ELLA immunoassay platform (ProteinSimple, San Jose, CA) was utilized to quantitate plasma IL-8 and PD-L1. Cox regression assessed hazard ratio (HR) for OS using both categorical (median) and continuous (log-transformed) biomarkers. Results: In univariate analysis, higher plasma IL-8 levels were significantly associated with reduced OS when analyzed as a continuous variable (HR = 1.53; p = 0.003) and were of borderline significance at the median cutpoint (HR = 1.32; p = 0.069; 20.9 vs 31.5 mos median OS). Plasma PD-L1 levels were not significantly associated with OS when analyzed as a continuous variable (p = 0.17), but increased levels were significant when analyzed at the median cutpoint (HR = 1.36; p = 0.044; 21.9 vs 29.0 mos median OS). When plasma IL-8 and PD-L1 levels were combined (median cutpoints), plasma IL-8 high / PD-L1 high patients (n = 58) had a significantly shorter OS vs the plasma IL-8 low / PD-L1 low patients (n = 58) (HR = 1.69; p = 0.009; 19.3 vs 32.9 mos median OS, respectively). In multivariate analysis, when adjusted for biopsy Gleason score, age, PSA, and ECOG PS (all at time of blood draw), only high plasma IL-8 (on a continuous basis) was significantly associated with reduced OS (HR = 1.43; p = 0.019). Conclusions: In mCRPC patients, high plasma IL-8 and PD-L1 levels were associated with reduced OS (separately and combined). Circulating IL-8 and PD-L1 evaluation may inform prognosis in mCRPC and could be considered as biomarkers in future studies determining response to immune checkpoint inhibitor and anti-IL8 therapy.

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