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, 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

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.

Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
GVHD. Cumulative incidence of acute (A) and chronic (B) GVHD. In panel A, there were no patients censored before day 100.
Figure 2.
Figure 2.
Relapse, progression-free survival, and overall survival. Cumulative incidence of relapse, progression-free, and overall survival.

Source: PubMed

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