Two-pronged atorvastatin administration for prophylaxis of acute GVHD

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1. Atorvastatin administration for both healthy donors and recipients of matched sibling allogeneic hematopoietic cell transplantation (HCT) represents feasible and safe potential acute GVHD prophylaxis.

2. Further investigation is needed to determine the effectiveness of this strategy.

Evidence rating level: 2 (Good) 

Study Rundown: Acute graft-versus-host disease (GVHD) causes significant morbidity and mortality following allogeneic hematopoietic cell transplantation, occurring in up to 50% of patients receiving HLA-matched transplants. Current prophylaxis has only modest efficacy and may compromise donor T cell-mediated graft-versus-host effects and delay immune reconstitution. Studies with murine models have suggest that two-pronged atorvastatin therapy for both donors and recipients has synergistically protective effects against acute GVHD compared to donor or recipient treatment alone. Therefore, the purpose of this study was to evaluate the safety and feasibility of this approach.

The authors found that this two-pronged approach was not associated with significant toxicities or primary treatment failures. Furthermore, adherence to the regimen was strong, suggesting that this treatment could feasibly be applied in a clinical setting. Nevertheless, it should be noted that this phase II trial had a small sample size and lacked a control arm with which to compare the efficacy of this treatment. Further trials are required to evaluate the benefit, if any, this approach offers to these patients.

Click to read the article in JCO

Relevant reading: Impact of recipient statin treatment on graft-versus-host disease after allogeneic hematopoetic cell transplantation

In-Depth [phase II prospective cohort study]: For this prospective trial, the study authors enrolled patients with hematologic malignancies and HLA-matched adult sibling donors. Patients and donors with active infections, abnormal renal, hepatic, pulmonary or cardiac function, poor Karnofsky performance scores and history of atorvastatin intolerance or allergy were excluded. For acute GVHD prophylaxis arm, donors were given atorvastatin for at least 14 days. All patients received uniform GVHD prophylaxis with tacrolimus, methotrexate, and atorvastatin.  The primary end points were donor/patient safety and cumulative incidence of grade 2 to 4 acute GVHD at day +100. Secondary end points included cumulative incidence of grade 3 to 4 acute GVHD, chronic GVHD, disease relapse, nonrelapse mortality, progression-free survival and overall survival.

Though atorvastatin administration to both donors and recipients was not associated with grade 3 to 4 GVHD, cumulative incidence of grades 2 to 4 at days +100 and +180 were 3.3% (CI, 0.2%-14.8%) and 11.1% (CI, 2.7% to 26.4%). One year cumulative incidence of chronic GVHD was 52.3% (ci, 27.6% TO 72.1%). One-year cumulative incidence of nonrelapse mortality and relapse were 9.8% (CI, 1.4% to 28%) and 25.4% (10.9% to 42.9%). One year overall survival and progression-free survival were 74% (CI, 58% to 96%) and 65% (CI, 48% to 87%). Viral and fungal infections were uncommon.

By Monica Parks and Andrew Bishara

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