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

• Published in: Blood Vol. 136; no. 13; pp. 1499 - 1506
• Main Authors: Kornblit, Brian, Storer, Barry E., Andersen, Niels S., Maris, Michael B., Chauncey, Thomas R., Petersdorf, Effie W., Woolfrey, Ann E., Flowers, Mary E.D., Storb, Rainer, Maloney, David G., Sandmaier, Brenda M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.09.2020; American Society of Hematology
• Subjects: Aged; Clinical Trials and Observations; Cyclosporine - therapeutic use; Female; Graft vs Host Disease - etiology; Graft vs Host Disease - immunology; Graft vs Host Disease - prevention & control; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; HLA Antigens - immunology; Humans; Immunosuppressive Agents - therapeutic use; Incidence; Male; Middle Aged; Mycophenolic Acid - therapeutic use; Sirolimus - therapeutic use; Tissue Donors; Transplantation, Homologous - adverse effects; Transplantation, Homologous - methods
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2020005338

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. •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. [Display omitted]