1. Administering CMX001 at 100 mg twice weekly for post-hematopoietic cell transplant patients provides effective prophylaxis against cytomegalovirus (CMV) infection.
2. The incidence of adverse events, particular acute graft-versus-host disease and diarrhea, appear to be dose-dependent in patients receiving CMX001.
Evidence Rating Level: 2 (Good)
Study Rundown: There is currently no effective drug for CMV prophylaxis in patients that receive allogeneic hematopoietic-cell transplantation. CMV seropositivity in these patients portends an increased risk of transplant-related death. Current options for prophylaxis have undesirable nephrotoxic and myelosuppressive effects. In this study, CMX001 – an acyclic nucleoside – is a new drug that successfully provided prophylaxis against CMV infections in post-hematopoietic cell transplant patients. The optimal CMX001 regimen for prophylaxis was determined to be 100 mg twice weekly beginning after transplantation up to 13 weeks post-transplant. Limitations of this study include the unequal distribution of CMV-seropositive and CMV-seronegative patients within each group. Also, CMV serology alone could be a significant predictive factor in determining the success of prophylactic therapy regardless of the drug dose. However, subgroup analysis suggested that CMV-seronegative patients might benefit more from prophylaxis with CMX001 than CMV-seropositive patients. Further studies will be required to assess the long-term safety of this novel drug as well as the optimal prophylactic duration.
In-Depth [randomized, controlled trial]: This study enrolled 230 patients and randomized them into a placebo group or one of five groups receiving escalating CMX001 doses (40 mg weekly, 100 mg weekly, 200 mg weekly, 100mg twice weekly and 200 mg twice weekly). CMX001 was started between 14-30 days post-transplant and discontinued at 13 weeks post-transplant. The primary endpoint was failure to prevent progression of CMV infection within one week after stopping the study drug. The group that derived the most benefit received CMX001 at 100mg twice weekly. This group had a significantly lower rate of CMV events when compared to placebo (10% v. 37%; risk difference, -27 percentage points; 95%CI, -42 to -12, p=0.002). At this same dose, 4 of 9 (44%) patients who were CMV-seropositive at baseline were positive for CMV DNA during drug administration versus 0 of 41 patients who were CMV-seronegative at baseline. The most common serious adverse events reported at a higher frequency in the CMX001 groups included acute graft-versus-host disease, diarrhea, and pneumonia.
By Jonathan Liu, MD and Adrienne Cheung
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