Sirolimus with CSP and MMF as GVHD prophylaxis for allogeneic ..

RESEARCH ARTICLE| SEPTEMBER 24, 2020

Sirolimus with CSP and MMF as GVHD prophylaxis for allogeneic transplantation with HLA antigen–mismatched donors

Brian Kornblit, Barry E. Storer, Niels S. Andersen, Michael B. Maris, Thomas R. Chauncey, Effie W. Petersdorf, Ann E. Woolfrey, Mary E. D. Flowers, Rainer Storb, David G. Maloney, Brenda M. Sandmaier

Blood (2020) 136 (13): 1499–1506.

https://doi.org/10.1182/blood.2020005338

Key Points

Adding sirolimus to standard GVHD prophylaxis reduces acute GVHD after nonmyeloablative HLA antigen–mismatched donor transplantation.

Compared with historical control subjects, the reduced incidence of acute GVHD translates into a better overall survival.

Abstract

This trial aimed to evaluate the efficacy of sirolimus in addition to cyclosporine (CSP) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis after nonmyeloablative conditioning for HLA class I or II mismatched hematopoietic cell transplantation (HCT). Eligible patients had hematologic malignancies treatable by allogeneic HCT. Conditioning consisted of fludarabine (90 mg/m2) and 2 to 3 Gy total body irradiation. GVHD prophylaxis comprised cyclosporine, mycophenolate mofetil, and sirolimus. The primary objective was to determine whether the cumulative incidence of grade 2 to 4 acute GVHD could be reduced to <70% in HLA class I or II mismatched HCT. The study was closed on December 20, 2018. Seventy-seven participants were recruited between April 14, 2011, and December 12, 2018, of whom 76 completed the study intervention. Median follow-up was 47 months (range, 4-94 months). The cumulative incidence of grade 2 to 4 acute GVHD at day 100 was 36% (95% confidence interval [CI], 25-46), meeting the primary end point. The cumulative incidence of nonrelapse morality, relapse/progression, and overall survival was 18% (95% CI, 9-27), 30% (interquartile range, 19-40), and 62% (95% CI, 50-73) after 4 years. In conclusion, the addition of sirolimus to cyclosporine and mycophenolate mofetil resulted in a lower incidence of acute GVHD, thus translating into superior overall survival compared with historical results. This trial was registered at www.clinicaltrials.gov as #NCT01251575.

Subjects:

Clinical Trials and Observations, Transplantation

Topics:

donors, graft-versus-host disease, human leukocyte antigens, mismatch, rapamycin, allogeneic hematopoietic stem cell transplant, graft-versus-host disease, acute, transplantation, homologous, mycophenolate mofetil

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