Sirolimus And Post-Transplant Cyclophosphamide As Graft-Versus-Host Prophylaxis In Patients Undergoing Matched Allogeneic Peripheral Blood Stem Cell Transplantation

Context Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for high-risk malignancies, although graft-versus-host (GVH) disease limits optimal outcomes. Post-transplant cyclophosphamide (PTCy) is an effective agent for the prophylaxis of GVH due to its functional inhibition of alloreactive T-lymphocytes and may enable GVH prevention while preserving the graft-versus-tumor effect. Additional data are needed to inform the use of PTCy when using fully matched donors. Objective To determine the rate of GVH, relapse, and overall survival following allogeneic HCT from fully matched donors using sirolimus/PTCy as GVH prophylaxis. Design Retrospective data were collected on 14 consecutive patients transplanted with a fully matched donor between November 2016 and June 2018 who received PTCy (day +3–4) and sirolimus (day +5) for GVH prophylaxis. Data collected included age, disease risk, HCT-CI, GVH incidence and grade, 1-yr overall survival, median survival, and GRFS. Patients or Other Participants 14 consecutive patients transplanted at BMDACC who received GVH prophylaxis with sirolimus and PTCy. All received thiotepa/fludarabine/melphalan conditioning. Results Disease risk index was intermediate (9), high (3), or very high (2). 7 with AML, 5 with MDS/MPN. Median age 69 yrs (39–81). Donor-related in 4, unrelated in 10, and all PBSC. Median days on sirolimus: 53 (5–238). Median overall survival was 908 days. 1-yr OS was 64%, and NRM was 28%. There was 1 case of VOD/SOS, 3 infectious deaths, and 1 due to CVA. Relapse-free survival median: 861 days (17–1362) and GRFS median: 565 days (17–1362). Incidence of all-grade GVH was 42%, with no grade 3/4 GVH and 7% cGVH. One patient relapsed. Seven of the 14 patients remain alive and disease-free at the time of this abstract, with a median follow-up of 3 yrs. Conclusions GVH prophylaxis with PTCy and sirolimus led to a low rate of grade 3/4 GVH and cGVH within this population. Relapse risk remained low, suggesting preserved graft-versus-tumor effect. Infectious deaths may be related to the timing of immune reconstitution following PTCy. Additional data are needed to inform the use of PTCy in the setting of fully matched donors. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for high-risk malignancies, although graft-versus-host (GVH) disease limits optimal outcomes. Post-transplant cyclophosphamide (PTCy) is an effective agent for the prophylaxis of GVH due to its functional inhibition of alloreactive T-lymphocytes and may enable GVH prevention while preserving the graft-versus-tumor effect. Additional data are needed to inform the use of PTCy when using fully matched donors. To determine the rate of GVH, relapse, and overall survival following allogeneic HCT from fully matched donors using sirolimus/PTCy as GVH prophylaxis. Retrospective data were collected on 14 consecutive patients transplanted with a fully matched donor between November 2016 and June 2018 who received PTCy (day +3–4) and sirolimus (day +5) for GVH prophylaxis. Data collected included age, disease risk, HCT-CI, GVH incidence and grade, 1-yr overall survival, median survival, and GRFS. 14 consecutive patients transplanted at BMDACC who received GVH prophylaxis with sirolimus and PTCy. All received thiotepa/fludarabine/melphalan conditioning. Disease risk index was intermediate (9), high (3), or very high (2). 7 with AML, 5 with MDS/MPN. Median age 69 yrs (39–81). Donor-related in 4, unrelated in 10, and all PBSC. Median days on sirolimus: 53 (5–238). Median overall survival was 908 days. 1-yr OS was 64%, and NRM was 28%. There was 1 case of VOD/SOS, 3 infectious deaths, and 1 due to CVA. Relapse-free survival median: 861 days (17–1362) and GRFS median: 565 days (17–1362). Incidence of all-grade GVH was 42%, with no grade 3/4 GVH and 7% cGVH. One patient relapsed. Seven of the 14 patients remain alive and disease-free at the time of this abstract, with a median follow-up of 3 yrs. GVH prophylaxis with PTCy and sirolimus led to a low rate of grade 3/4 GVH and cGVH within this population. Relapse risk remained low, suggesting preserved graft-versus-tumor effect. Infectious deaths may be related to the timing of immune reconstitution following PTCy. Additional data are needed to inform the use of PTCy in the setting of fully matched donors.