Post Transplant Cyclophosphamide as GvHD Prophylaxis in Patients Receiving Mismatched Unrelated HCT: the PHYLOS trial.

• PTCY-based GVHD prophylaxis in HCT from a MMUD leads to a low rate of aGVHD, with a low incidence of NRM and acceptable relapse rate

Post-transplant high-dose cyclophosphamide (PTCy) is effective in overcoming the negative impact of HLA disparity in the haploidentical setting. In the light of these results, we investigated the efficacy and safety of PTCy, with a calcineurine inhibitor and mycophenolate mofetil, in improving clinical outcomes of haematopoietic cell transplantation (HCT) from mismatched unrelated donor (MMUD) in patients with acute myeloid malignancies by reducing aGvHD incidence and severity. A prospective single arm, phase II study (PHYLOS - NCT03270748) was conducted by the Italian GITMO. The primary objective was the cumulative incidence (CI) of grade II-IV aGvHD. Conditioning regimen for all patients was busulfan (total dose 12.8mg/kg) and fludarabine (total dose 160mg/m2). The ethical committees of the participating centers approved the study (EURODRACT 2017-003530-85). Seventy-seven consecutive patients (AML: 64; MDS: 13) were enrolled at 26 Italian transplant centers (January 2020-November 2022). Median age was 53 years (range 19-65). The 100-day cumulative incidence (CI) of grade II-IV aGvHD was 18.2% (95%CI: 10.6-27.6) and 6.5% (95%CI: 3.1-15.1) for grade III-IV. Seventy-one patients (92%) had full-donor chimerism with complete neutrophil engraftment by day +30.One-year CI of chronic GvHD (cGvHD) was 13.4% (95%CI: 6.9-22.1). One-year CI of non-relapse mortality was 9.1% (95%CI: 4.0-16.9), and the relapse rate was 23.8% (95%CI: 14.9-33.9). One-year overall survival and graft-relapse-free survival were 78.6.% (95%CI: 67.4-86.3) and 55.3% (95%CI: 43.4-65.7), respectively. Our study in a homogeneous patient cohort suggests that PTCy leads to a low rate of aGvHD and improves clinical outcomes of MMUD transplantation.