Adding sirolimus to the standard therapy of cyclosporine and mycophenolate mofetil may reduce the incidence of graft-versus-host disease (GVHD) in patients receiving hematopoietic stem cell transplantation (HSCT) for advanced hematologic malignancies, according to results reported in the Lancet Haematology.

In this phase 3 trial, 180 patients with advanced hematologic malignancies treatable by HSCT were randomly assigned to receive cyclosporine and mycophenolate mofetil either with or without sirolimus. Of these, 167 patients were included in the efficacy and safety analyses. A total of 77 patients received the standard regimen, and 90 received the experimental regimen that included sirolimus.

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The cumulative incidence of grade 2 to 4 acute GVHD within 100 days was 26% in the triple-drug group and 52% in the standard drug group (hazard ratio [HR], 0.45; P =.0013). In the sirolimus group, nonrelapse mortality was 4% after 1 year and 16% after 4 years. In the control group, nonrelapse mortality was 16% after 1 year and 32% after 4 years (HR, 0.48; P =.021).

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The rate of progression-free survival was 77% at 1 year and 64% at 4 years in the sirolimus group. In the control group, the rate of progression-free survival was 59% at 1 year and 41% at 4 years (HR, 0.64; P =.045).

The researchers noted that the survival benefits seen in the study seemed “to be driven by the reduced cumulative incidence of grade 2 to 4 acute GVHD and nonrelapse mortality without increasing the risk of relapse.”

The triple-drug therapy yielded no major differences in nonhematopoietic toxicity at day 100, with 25% of patients in the triple-drug group experiencing adverse events compared with 34% of patients in the standard group (P =.52).

Because adding sirolimus to the standard of care reduced acute GVHD and improved survival, the researchers suggested that this therapy should be considered the new standard for GVHD prevention after HSCT with nonmyeloablative conditioning.


1.     Sandmaier BM, Kornblit B, Storer BE, et al. Addition of sirolimus to standard cyclosporine plus mycophenolate mofetil-based graft-versus-host disease prophylaxis for patients after unrelated non-myeloablative haemopoietic stem cell transplantation: a multicentre, randomised, phase 3 trial [published online June 24, 2019]. Lancet Haematol. doi:10.1016/S2352-3026(19)30088-2