P11.78.A BIUXX

Abstract

Abstract BACKGROUND Glioblastoma (GBM) is a tumor with dismal prognosis and the definition of novel therapeutic targets is a pressing matter in neuro-oncology. Several groups reported the presence of Cytomegalovirus (CMV) in GBM. This virus establish a life-long infection in the host and is able to induce the hallmarks of cancer. Thus, antiviral therapy targeting CMV may represent a valid therapeutic option for patients with GBM. Over the last 15 years we treated more than 150 patients with GBM at Karolinska Universiy Hospital with the antiviral drug valganciclovir as an add-on to standard therapy. We compared retrospectively survival of these patients with contemporary controls with similar clinical and demographic characteristics treated only with standard therapy and found that patients receiving the antiviral seemed to survive longer. In addition to the direct oncomodulatory effect of CMV in GBM cells, its reactivation may affect negatively fragile individuals such as patients with GBM. Indeed patients serologically positive for CMV survives shorter time compared to serologically negative patients. Also Goerig et al. showed that CMV may also be reactivated during irradiation of the brain and cause life threating encephalitis in as many as 48% IgG positive patients with brain tumors. This was linked to encephalopathy and to early mortality risk. Thus, a successful therapeutic strategy would be to start antiviral therapy before or concomitantly radio-chemotherapy since antiviral drugs could prevent CMV reactivation before the virus would be able to cause neurologic deterioration. MATERIAL AND METHODS we analyzed by prospectively collected serological data (IgG and IgM) for CMV of 42 patients with GBM treated with valganciclovir (n=22) or placebo (n=20) in a double blind setting before, during and after radio-chemotherapy and at 6 and 12 months follow ups. We built contingency table and performed Fisher´s exact test. RESULTS At the end of radiation therapy, 5 of 12 (41.6%) IgG positive patients in the placebo group were also IgM positive, showing an active/recent infection, while none of the 16 patients were IgM positive in the valganciclovir treated group (p=0.0067). Three of the 5 patients with CMV reactivation in the placebo group experienced also neurological deterioration and developed an early recurrence at just 3 months while none developed early recurrence in VGCV group. CONCLUSION Valgancicovir prevented CMV reactivation in patients with GBM undergoing chemo-radiotherapy in a prospective, randomize setting. Prophylactic antiviral treatment may therefore be used to prevent encephalopathy and to early mortality risk linked to CMV reactivation. The clinical value of these results will need to be confirmed in larger studies. In this regard, a randomized trial evaluating anti-CMV therapy in 220 patients with GBM (the VIGAS 2, NCT04116411) is currently ongoing at our institution.