Cellular Immunotherapy For Refractory Hematological Malignancies.

7039 Background: Allogeneic cellular infusion is a potent immune stimulus. We present data from our FDA approved IND Phase II clinical trial (BrUOG 273) where allogeneic haploidentical lymphocytes are infused without prior chemotherapy or radiation to create a rejection response that hypothetically breaks host tumor tolerance. Methods: Eligible patients have relapsed or refractory acute leukemia. HLA haplo donors undergo leukapheresis without G-CSF priming. 1-2x108CD3+ cells/kg were infused unprocessed immediately after collection. Peripheral blood collected 1-4, 8-24, 34-48, 72-96 and 168-192 hours post infusion were examined for effector cell populations, stimulatory/inhibitory signals, and cytokine release profiles. Wilcoxon rank sum tests were used for statistical analysis. Results: Five patients were infused haplo donor cells. Four developed hyperpyrexia post infusion that lasted 24-48 hours (median T 0-4 hours post infusion 98°F, median Tmax 8-192 hours post infusion 102.4°F, p = 0.009). Host CD8 T cells demonstrated decreased perforin expression post compared to pre-infusion (median pre 77.6%, median post 61%, p = 0.03) with no changes in granzyme A/B, LAMP1, or FasL expression. Rapid up-regulation of PD-1 on host CD8 T cells (median pre 5.6, median post 49.7, p = 0.005) was present. Non-statistically significant upregulation of PD-1 ligands occurred on leukemic blasts from 0-4 to 34-48 hours post infusion. Cytokine release profiles post infusion showed high IL-10 (median 86pg/mL) with low IFNg (median < 1pg/mL) and IL-6 (median 7.47pg/mL) levels. One of five patients demonstrated a decrease in marrow blast counts post therapy (43% pre to 21% 4 weeks post infusion). No dose limiting toxicities or durable chimerism was seen. Conclusions: Haplo cellular infusions are well tolerated and show biological activity in relapsed AML. One of five patients had a reduction in marrow blasts with haplo infusion alone. Host CD8 T cells were less activated post infusion compared to pre-infusion and increased inhibitory PD-1 expression post infusion. Cytokine release profiles were more anti-inflammatory than those previously described. Greater initial CD8 T cell activation +/- immune checkpoint inhibitory blockade may improve efficacy. Clinical trial information: NCT01685606.