In this single center retrospective cohort study, subjects treated with or without Imatinib had similar rates of clinical CMV. In addition to demonstrating no overall effect on reactivation, Imatinib did not appear to alter more clinically significant CMV endpoints, such high viral load and CMV disease.
Published studies have differed in their interpretation of the antiviral and immune effects of Imatinib [1
]. Imatinib has been shown to inhibit the process of CMV internalization through TK inhibition [2
], while clinical studies have demonstrated increased rates of VZV in those treated with Imatinib [4
]. Other studies have shown adverse effects on the immune response including a reversible lymphopenia and hypogammaglobulinemia [9
], and dose dependent inhibition of T cell-receptor-mediated T cell activation and proliferation [10
]. Further complicating these data are reported effects on dendritic cells (DC). While some studies demonstrate negative effects such as lower responses of Imatinib exposed DCs against tumor and recall antigens [11
], others have shown enhanced presentation of antigen by DCs exposed by Imatinib [1
Our study is the first to assess the effect of Imatinib on CMV in a clinical setting, and these data fail to show alterations in CMV outcomes in those receiving Imatinib therapy. It is possible that Imatinib may need to be given earlier during the at-risk period to provide therapeutic benefits, or since Imatinib may prevent viral entry, it may be more important in primary infection. Finally, the antiviral effects of Imatinib may be overshadowed by the drug’s adverse effects on the immune response.
The major limitation of this study was sample size, which hampered our ability to detect less prominent antiviral effects of Imatinib. We project that a 55% reduction in CMV reactivation was needed in order to detect a difference in treatment groups. To put this in context, ganciclovir prophylaxis reduces CMV reactivation measured by antigenemia by 70–80%. Thus, while our study was not able to detect a moderate antiviral effect of Imatinib, we had enough power to detect effects similar to those seen in presently used antiviral drugs. Because we completed time-to-event analyses based on weekly screening, it is possible that more frequent sampling could provide additional information on viral kinetics not available in these data. In order to clarify the role of immunosuppressive effects of Imatinib, additional information on lymphocyte recovery and incidence of lymphopenia will also be important to address in future studies. In contrast to these limitations, this study was strengthened by the high rate of CMV endpoints, the accuracy of data collection, and the use of standardized supportive care strategies in our population.
In summary, in this initial study, we were unable to demonstrate a major affect of Imatinib on CMV reactivation in this single center cohort of HCT recipients. While our data could not confirm a strong anti-CMV effect of the drug, larger studies would be needed to accurately define if there are smaller effects of Imatinib or other TK inhibitors on CMV, and to fully understand their potential role as primary or adjunctive antiviral therapy.