Letermovir Prophylaxis Demonstrates High Efficacy in Adult Cytomegalovirus (CMV) Seropositive Cord Blood Transplant (CBT) Recipients: A Comparison with Pre-Letermovir Era CBT Controls

Abstract

Background CMV seropositive CBT recipients have a high risk of CMV infection. Early pre-emptive therapy is required to avoid CMV disease but is associated with significant toxicities. Methods This analysis compares the day +100 incidence & severity of clinically significant CMV infection (viremia leading to pre-emptive treatment or disease) in CMV seropositive CBT adult patients (pts) who received letermovir prophylaxis transplanted 12/2017-6/2018 vs historic controls transplanted 3/2013-12/2017. Control pts received ganciclovir prophylaxis days -7 to -2 then standard dose acyclovir. Letermovir pts received standard dose acyclovir & started letermovir IV or PO on day +7 & continued beyond day +100. All pts received uniform intermediate intensity Cy 50 mg/kg / Flu 150 mg/m2/ Thio 5-10 mg/kg / TBI 400 cGy conditioning with CSA/ MMF. Pts were monitored by qPCR twice weekly from approximately day +14-60 & then 1-2 x/weekly days +60-100. Results 62 [median age 51 years (range 23-66), 46 leukemia, 7 MDS/ MPD, 9 NHL/ HL] historic control pts received double unit grafts with a median unit-recipient HLA-allele match of 5/8 (range 2-7). By day +100, 51 pts developed clinically significant CMV infection for a day +100 cumulative incidence of 82% (95%CI: 70-90). The median viremia onset was 34 days (range 5-74) & 5 pts developed CMV disease by day +100 (3 pulmonary, 2 GI). Initial therapy was with foscarnet in 28 pts & ganciclovir/ valganciclovir in 23. Clinically significant therapy toxicities (renal &/or myelosuppression) were observed in 38/51 (75%) pts (Table 1). By day +100, CMV caused or contributed to 3 pulmonary deaths. 10 pts [median age 48 years (range 24-59), 9 leukemia, 1 MDS/ MPD, median 5/8 (range 3-6) unit-recipient HLA-match] received letermovir prophylaxis (8 IV, 2 PO) (Table 2). All pts engrafted. The day +100 cumulative incidence of clinically significant CMV infection was 0% (p Conclusions This analysis suggests letermovir prophylaxis is highly effective at mitigating CMV disease, CMV-related mortality, & the need for toxic CMV therapies. Moreover, it has been well tolerated in CBT recipients. While further detailed investigation in a larger population is required, this data is very promising & the extent of the benefit suggests that letermovir could be a cost-effective new standard of care in adult CBT. The duration of needed prophylaxis beyond day +100 in CBT recipients also requires investigation.