Phase II study on maraviroc for the prevention of graft-versus-host disease

Ran Reshef from Abramson Cancer Center and the Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, and colleagues conducted a phase II trial to evaluate the efficacy of maraviroc in combination with conventional graft-versus-host disease (GvHD) prophylaxis in patients with hematological malignancies who received reduced-intensity conditioning and underwent unrelated donor allogeneic hematopoietic stem cell transplantation (allo-HSCT). The findings were published in the Biology of Blood and Marrow Transplantation.

Primary endpoint was the cumulative incidence of grade 2–4 acute GvHD by day 180. Conditioning regimen contained fludarabine (i.v. 120 mg/m²) and busulfan (i.v. 6.4 mg/kg) (Flu/Bu), followed by granulocyte colony-stimulating factor mobilized peripheral blood stem cell graft from an unrelated donor on day 0. Patients (n = 37; median age = 64 years [range, 49–72]) received GvHD prophylaxis regimen including tacrolimus (0.06 mg/kg/d in 2 divided doses starting on day –3) and methotrexate (i.v. 15 mg/m² on day 1 and 10 mg/m² on days 3, 6 and 11). Patients received oral maraviroc twice daily from day –3 until day 90.

Key findings:

Safety

• Eight patients did not finish treatment due to the following events: disease relapse and early withdrawal of all GvHD prophylactic agents (n = 5), skin reaction that was thought to be related to sulfa but maraviroc was discontinued as well (n = 1), early infection-related death (n = 1) and poor oral tolerance (n = 1)
• One patient’s dose was reduced to 150 mg twice daily due to orthostatic hypotension

Efficacy

• Day-180 incidence of grade 2–4 acute GvHD: 22 ± 7% (95% CI, 8–36)
• 1-year incidence of moderate to severe chronic GvHD: 8 ± 5%
• 1-year non-relapse mortality: 11 ± 5%
• 1-year disease relapse: 30 ± 8%
• 1-year GvHD-free/relapse-free survival: 46 ± 8%
• 1-year overall survival: 70 ± 8%
• N = 20 patients are alive; n = 19 of these achieved complete remission

3-month course vs 1-month course of maraviroc

• GvHD-free/relapse-free survival was significantly better in patients who received maraviroc for three months vs those who received it for one month: adjusted HR = 0.45 (95% CI, 0.25–82), P = 0.009

Impact of day 0 maraviroc concentration on outcomes

• Maraviroc concentrations above the median on day 0, significantly associated with lower incidence of grade 2–4 acute GvHD rates: 4% vs 36% at 6 months; adjusted HR = 0.33 (95% CI, 0.12–87), P = 0.025

In conclusion, maraviroc, administered for three months, efficiently prevents acute and chronic graft-versus-host disease. Survival and GvHD-free/relapse-free survival were superior in patients who received maraviroc for three months compared with patients who received one month of maraviroc. Higher day 0 maraviroc concentrations showed significant correlation with lower rates of acute GvHD.