Quality of Life in Patients Treated with Sirolimus and Tacrolimus for Prevention of GRAFT-Versus-HOST Disease

Background:  Several recent studies have examined the use of sirolimus (SIR) and tacrolimus (TAC) for prevention of graft-versus-host disease (GVHD).  Data are sparse, however, regarding patient-reported quality of life (QOL) associated with this regimen.  We report an analysis of QOL outcomes in the first year post-transplant from a randomized controlled trial of (SIR/TAC) compared to methotrexate (MTX)/TAC.

Methods:  Allogeneic hematopoietic cell transplant (HCT) patients randomized to SIR/TAC received one year of SIR following HCT, while MTX/TAC patients received MTX on days 1, 3, 6, and 11. QOL was assessed with the Functional Assessment of Cancer Therapy – Bone Marrow Transplant Treatment Outcome Index (TOI) prior to HCT and day 30, 90, 180, 270, and 360 following HCT.  Random effects models were used to examine longitudinal trajectories of QOL between day 30 and 360 by study arm, controlling for baseline TOI scores. 

Results:  A total of 74 patients were enrolled (37 per study arm); all contributed data to these analyses.  Analyses indicated that the MTX/TAC group showed greater improvement in TOI scores over time compared to the SIR/TAC group (p=.02); by day 360, the average difference between groups was 7.18 points (p=.03).  This effect continued to be significant (p<.01) when controlling for clinical differences between groups, including acute GVHD, chronic GVHD, and anemia.  Exploratory analyses of subscales comprising the TOI [i.e., Physical Well-Being (PWB), Functional Well-Being (FWB), BMT Scale (BMTS)] indicated that group differences were due to greater improvement in PWB in the MTX/TAC group (p=.02).  Additional exploratory analyses of items on the PWB scale indicated that members of the SIR/TAC arm were more likely to endorse a lack of energy and nausea over time (ps≤.01).  Study arm differences on these items persisted when controlling for acute GVHD, chronic GVHD, and anemia (ps<.01).

Conclusions:  Data from the current study indicate that SIR/TAC is associated with less improvement in QOL in the first year post-HCT compared to MTX/TAC.  This difference is not attributable to other potential clinical differences between study arms, including acute and chronic GHVD and anemia.  Differences in QOL appear to result in part from greater fatigue and nausea in participants treated with SIR, which was administered throughout the one year follow-up period.