A Single-Institution Randomized Prospective Trial of Pre-Emptive Therapy with Oral Valganciclovir Compared with IV Ganciclovir for Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplant (aHSCT), Delayed until Viral Load (VL) >10,000 Copies/Ml or >5,000 Copies/Ml X 2

Background: CMV remains a major cause of morbidity and mortality after aHSCT. The current standard of care for pre-emptive treatment of CMV viremia is IV ganciclovir (GCV). Oral valganciclovir (VGV) has been shown to be effective for the treatment of CMV retinitis in patients with HIV, and offers the advantage of oral administration. This prospective randomized clinical trial was designed to compare VGV to GCV as pre-emptive therapy for CMV viremia in the post-aHSCT population.

Methods: Pts undergoing aHSCT at risk for CMV viremia, determined by donor and/or recipient CMV positivity, were monitored post-aHSCT by weekly quantitative whole-blood PCR. Due to concerns about oral absorption, pts with Grade III/IV gut GVHD were excluded. Positivity was determined by a VL >10,000 copies/mL or >5,000 copies/mL X 2. Pts were randomized to receive either: GCV 5mg/kg BID for 7 days followed by daily GCV 5mg/kg for 7 days or VGV 900mg BID for 7 days followed by 900mg daily for 7 days. At 14 days, PCR was reassessed. Pts with VL <5000 copies/mL completed a 21 day course of daily GCV or VGV. Pts with VL >5000 copies/mL but < initial value completed a 28 course of daily GCV or VGV. Pts with VL > initial value returned to BID GCV or VGV to complete a 28 day course (pts with 21 day level > day 14 level were removed from the study). Primary endpoint was clearance of viremia (VL <5000 copies/mL) within 28 days of initiation of therapy.

Results: 37 pts were enrolled and 19 pts received treatment with VGV while 18 pts received treatment with GCV. Patient characteristics were as follows: median age was 53 (range 18–64); 25 males, 12 females; 25 pts had myeloablative conditioning regimens, 12 had non-myeloablative conditioning; 28 pts had unrelated donors, 9 had matched sibling donors; 32 pts received peripheral blood stem-cell products, 5 received bone marrow stem-cell products. These baseline characteristics were equally distributed across the two arms.

Results: VGV and GCV showed equivalent efficacy as pre-emptive therapy (Table below). Toxicities were similar between the two arms: there were 35 grade III/IV events in the VGV arm and 42 grade III/IV events in the GCV arm. There were 20 grade III/IV hematologic toxicities in the VGV arm with 2 grade III episodes of neutropenia and 1 grade III febrile neutropenia. In the GCV arm, there were 23 grade III/IV hematologic toxicities, with 3 grade III episodes of neutropenia and 2 febrile neutropenic events. There were 2 deaths not related to the study medications or CMV. No patients developed CMV disease.

Conclusions: In this trial VGV was equivalent to GCV with regard to clearance of viremia at 28 days. VGV can be considered an alternative pre-emptive therapy for CMV viremia post-aHSCT in patients without evidence of grade III/IV GVHD of the gut.