Primary letermovir prophylaxis prevents cytomegalovirus reactivation after haploidentical allogeneic HSCT
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ORLANDO — The novel antiviral agent letermovir appeared effective for primary cytomegalovirus prevention among haploidentical stem cell transplant recipients, according to results of a single-center chart review presented at TCT | Transplantation & Cellular Therapy Meetings.
“Historically, if these patients get nothing, cytomegalovirus [CMV] reactivation rates within 100 days would be around 60% to 66%. In our study, reactivation rates were just shy of 18%, so we know this drug works,” Omik Patel, PharmD, BCOP, clinical pharmacist in the bone marrow transplant and cellular therapy program at The University of Kansas Health System, told Healio.
CMV is a common complication among patients who undergo allogeneic HSCT. Reactivation has been linked to a variety of complications after transplant, including acute and chronic graft-versus-host disease, graft failure, multiorgan failure, bacterial and fungal infections, and higher mortality risk.
A prior study demonstrated the potential effectiveness of letermovir prophylaxis. However, more than two-thirds of that study population received matched-unrelated or matched-sibling donor transplants.
“We thought the haploidentical population was a bit underrepresented at around 16%,” Patel said. “We really wanted to look at that population because they are at slightly higher risk for CMV reactivation.”
Patel and colleagues evaluated incidence of CMV reactivation before and after day 100 among 28 CMV seropositive haploidentical HSCT recipients (median age, 52.5 years; range, 23-73; 50% men) who received letermovir as primary prophylaxis between May 2018 and December 2019.
Seventeen patients (60.7%) had CMV seropositive donors. The primary indications for HSCT included acute myeloid leukemia (50%), myelodysplastic syndrome (14.3%), severe aplastic anemia (7.1%) or other disease (28.6%).
Sixteen patients (57.1%) received stem cells derived from peripheral blood and 12 (42.9%) received stem cells derived from marrow.
The majority of patients underwent reduced-intensity conditioning with fludarabine, cyclophosphamide and total body irradiation.
Patients received letermovir prophylaxis from day 16 to day 100. They subsequently received high-dose valacyclovir — administered in 2 g doses three times a day — through day 365.
Patel and colleagues used polymerase chain reaction testing starting on day 20 to monitor CMV titers. Monitoring occurred twice weekly through day 100, followed by weekly thereafter until day 365.
Investigators initiated preemptive therapy with a CMV threshold of at least 125 IU/mL between day 20 and day 100, and at least 250 IU/mL after day 100.
Patients who experienced CMV reactivation while on letermovir switched to high-dose valacyclovir prophylaxis through day 365.
Five patients (17.8%) developed CMV reactivation prior to day 100 (median, day 28; range, 24-67). However, because most reactivations occurred early, it is difficult to determine whether patients already had reactivation prior to letermovir prophylaxis, Patel said.
“Letermovir bioavailability is approximately 25% after HSCT; therefore, a majority of patients are not receiving maximum benefit at the start of treatment, which could have led to the high amount of reactivation seen early on in our study,” researchers wrote in the abstract.
Of the remaining 23 patients, five (21.7%) developed CMV reactivation after discontinuation of letermovir at day 100 (median, day 138; range, 117-156). This increase was not significant.
“The high-dose valacyclovir could’ve helped keep these numbers down,” Patel told Healio.
Researchers reported no cases of CMV disease.
Median time to neutrophil engraftment was 17 days.
One patient with CMV reactivation developed GVHD that required treatment with high-dose corticosteroids.
Researchers acknowledged limitations to their study, including its retrospective nature, small sample size and lack of a comparator group.
However, the results support the efficacy of primary letermovir prophylaxis for preventing CMV reactivation, researchers concluded.
Given the increased CMV reactivation rate after day 100, letermovir potentially could be used as secondary prophylaxis, according to researchers.
Future studies should assess the ideal duration of prophylaxis for this high-risk group, as well as compare reactivation rates between patients who receive letermovir or high-dose valacyclovir, Patel said. – by Mark Leiser
Reference: Patel O, et al. Abstract 515. Presented at: TCT | Transplantation & Cellular Therapy Meetings; Feb. 19-23, 2020; Orlando.
Disclosures: Patel reports no relevant financial disclosures. One author reports a speakers bureau role with Seattle Genetics. Another author reports an advisory board role with Juno Therapeutics, as well as advisory board and speakers bureau roles with Kite Pharma.