The Combination of Siromilus Plus Tacrolimus (SiTac) Improves the Results of Cyclosporine Plus Mycophenolate Mofetil (CsAMMF) After Reduced Intensity Conditioning (RIC) Unrelated Donor Allogeneic Transplantation

One of the most extensively used approaches to prevent GVHD in the RIC setting is the combination of CsAMMF. Other strategies have been described such as SiTac, mostly as single center experiences, with promising results. Nevertheless, data from multicenter studies are lacking using the latter approach and, furthermore, no studies have been performed comparing both approaches.

in the current study we describe the results of the prospective multicenter trial 2007–006416-32 by GEL-TAMO/GETH using SiTac as GVHD prophylaxis and compare this approach to the combination of CsAMMF in a sequential analysis.

Material and Methods: from May 2002, 90 patients were included. All of them received an URD transplantation after RIC based on fludarabine (150 mg/m²) plus busulphan (10 mg/kg) or melphalan (140 mg/m²). 45 transplanted between 2002 a 2007 received CsAMMF as GVHD prophylaxis while the remaining 45 patients undergoing transplantation from 2008 received SiTac. 41% of the patients were in CR, 30% were in PR and 29% had active disease at the time of transplantation. No differences were observed in terms of disease status. Patients in the SiTac trial had a higher median age (49 versus 43 years, p=0.02) while a higher percentage of patients in the CsAMMF were diagnosed with acute leukemia (10 versus 19 patients, p=0.05). Supportive care was similar in both subgroups except for the use of azols as antifungal prophylaxis which was not allowed in the SiTac.

12% of patients receiving SiTac developed mycroangiopathy which required to modify immunesuppresive treatment although it did not increase the mortality of the procedure. No VOD was reported. No significant differences were observed neither in terms of hematopoietic recovery nor in the cumulative incidence of grades 2–4 or 3–4 aGVHD (49% versus 50% grades 2–4 and 15% versus 26% grades 3–4 for patients receiving SiTac versus CsAMMF, respectively). By contrast 18% of patients receiving SiTac versus 55% of those receiving CsAMMF developed gut aGVHD ≥ grade 2, p=0.007. Cumulative incidence of cGVHD was 55% versus 88% for SiTac versus CsAMMF, respectively, p=0.0002 while the incidence of extensive cGVHD was 27% versus 52%, respectively, p=0.03. Non relapse mortality was 10% versus 20% at 100 days and 19% versus 40% at 1 year, for patients receiving Si-Tac versus CsAMMF, respectively (p=0.028). Event free and overall survival at 2 years were 59% versus 35%, p=0.008 and 72 versus 48%, p=0.018, for patients receiving Si-Tac versus CsAMMF, respectively.

the current study confirms in a multicenter trial the promising results of the combination Sirolimus plus Tacrolimus among patients undergoing RIC URD transplantation. The current is the first study comparing in a sequential study SiTac versus CsAMMF and confirms that the prior decreases the risk of chronic GVHD and the non-relapse mortality of the procedure which translates into a better event free and overall survival.

No relevant conflicts of interest to declare.