Respiratory syncytial virus in hematopoietic cell transplant recipients and patients with hematologic malignancies

Khawaja, Fareed; Chemaly, Roy F.

As previously discussed, there are limited therapeutic options for RSV infections and new therapies are desperately needed. Presatovir is an oral RSV fusion inhibitor with selective anti-RSV activity in vitro. In a phase I, firstin-human, single-and multiple-ascending dose study, 98 presatovir had an excellent safety profile, despite having an extended half-life. The oral bioavailability was also good, regardless of prandial state. 98 Although clinical trials on RSV infections in transplant recipients have been challenging due to low recruitment, 71 two phase II trials on presatovir in HCT recipients with RSV infections were recently completed 99, 100 (ClinicalTrials.gov number NCT02254408). To overcome potential low recruitment, 189 HCT recipients with RSV infections limited to the upper respiratory tract were recruited from a total of 43 centers in nine countries over 2.5 years. 99, 100 Preliminary data showed that presatovir was not effective at reducing nasal RSV viral load over time or at reducing the incidence of lower respiratory tract complications. However, in an exploratory analysis, presatovir did reduce the rate of progression to lower respiratory tract complications in patients with lymphopenia relative to the rate in placebotreated patients. Furthermore, presatovir was not effective at reducing nasal RSV viral load, supplemental oxygen use or all-cause mortality in another phase II trial in HCT recipients with RSV LRTI. 99, 100 Several lessons were learned from the two trials. HCT recipients with one or more risk factors (i.e. lymphopenia, neutropenia, or infected within a year from transplant) for poorer outcomes from RSV infections may benefit the most from an effective antiviral therapy. On the other hand, time from symptom onset and time before the development of lower respiratory tract complications are probably critical factors in determining the effectiveness of fusion inhibitors.