De-Escalation of Ptcy Dosing in Matched Allogenic Transplants: A Single Institution Retrospective Study

Introduction The role of post-transplant cyclophosphamide (PTCy) in preventing acute GVHD (aGVHD) and chronic GVHD (cGVHD) has been well established in the haploidentical setting (Al-Homsi AS et al., Post-transplant high-dose cyclophosphamide for the prevention of graft-versus-host disease. Biol Blood Marrow Transplant. 2015;21(4):604-611). More recently, several studies are also supporting its use in matched related and unrelated donors (Williams L et al., Post-transplantation Cyclophosphamide: From HLA-Haploidentical to Matched-Related and Matched-Unrelated Donor Blood and Marrow Transplantation. Front Immunol. 2020;11(April):1-7). But as new emerging data are starting to show some toxicities from that regimen, a reevaluation of the optimal PTCy dose is highly valuable (Duléry R et al., Early Cardiac Toxicity Associated with Post-Transplant Cyclophosphamide in Allogeneic Stem Cell Transplantation. JACC CardioOncology. 2021;3(2):250-259; Goldsmith et al., Posttransplant cyclophosphamide is associated with increased cytomegalovirus infection: a CIBMTR analysis. Blood. 2021;137(23):3291-3305). PTCy dose de-escalation in preventing GvHD was also evaluated in a phase I/II study (NCT03983850) with initial results indicating that de-escalation of PTCy (DL2, 25 mg/kg/day given in Days 3−4) may provide a feasible and effective approach in preventing severe aGvHD(McAdams MJ et al., Phase I Study De-Intensifying Exposure of Post-Transplantation Cyclophosphamide (PTCy) after HLA-Haploidentical Hematopoietic Cell Transplantation (HCT) for Hematologic Malignancies. Transplant Cell Ther Off Publ Am Soc Transplant Cell Ther. 2021;27(3): S9-S11). However, this was in the setting of haplo-identical transplants. Currently there are no studies that investigate the safety and efficacy of a lower dose of PTCy in matched allogenic transplants. Methods We retrospectively selected 37 consecutive patients who underwent transplant at our center from January 2017 to April 2021. Patients who received a mismatched or haploidentical transplants were excluded. 26 matched sibling or matched unrelated donor transplants were further analyzed. These were divided into 3 cohorts according to GVHD prophylaxis: cohort 1 (No-PTCy) received standard calcineurin inhibitor-methotrexate based GVHD prophylaxis (n=16), cohort 2 (PTCy-50) received PTCy at 50 mg/kg (D+3 and D+4) in combination other immunosuppressive drugs (ISD) (n=6), and cohort 3 (PTCy-25) received PTCy at 25 mg/kg (D+3 and D+4) in c