Background: Cytomegalovirus (CMV) is associated with significant morbidity and mortality in allogeneic hematopoietic cell transplantation (allo-HCT) patients (pts). Cumulative incidence of CMV infection in high-risk patients such as CD34-selected or haploidentical HCT have been reported as high as 61.8-84.5% and 53-81%, respectively. Letermovir (LTV) was approved in 11/2017 for prophylaxis (ppx) in CMV-seropositive recipients (R+) of allo-HCT. Since 12/2017, LTV ppx was implemented at our center for both primary and secondary ppx. We report our real-world experience. Methods: Adult CMV R+ allo-HCT pts who initiated LTV as primary or secondary prophylaxis were identified between 1/1/2018 and 6/30/18. Cord blood transplants were excluded. The primary outcome was the incidence of clinically significant CMV infection (CMV viremia requiring preemptive treatment or CMV disease). Pts were followed through 9/2018. Results: 53 pts initiated LTV. 69.8% pts were at high risk for CMV reactivation and disease (primarily ex vivo T-cell depleted HCT [n = 18; 34%] or haploidentical T-replete HCT [n = 12; 22.6%]). Baseline characteristics are summarized in Table 1. 39 pts (73.5%) received LTV as primary ppx after HCT, with a median day of LTV initiation of D+7 (range D+7À ÀD+40). At LTV initiation, 34 pts had an undetectable CMV DNA, and 4 had CMV <137 IU/mL. Clinically significant CMV infection requiring preemptive treatment occurred in 2 of 39 pts (5.1%). One patient was treated with valganciclovir (VGV) for persistent CMV < 137 IU/mL. LTV was then used as secondary ppx. A 2nd patient, developed persistently detectable CMV (<137 IU/mL) and breakthrough CMV viremia with a mutation in UL56 at site C325YLTV successfully treated with VGV. The median duration of primary LTV ppx was 116 days (54-221), with primary ppx continuing beyond 14 weeks post HCT in 29 pts. If LTV was discontinued the median additional follow-up was 40 days (0-154), without clinically significant CMV infection to date. An additional 15 pts* (26.4%) received LTV as secondary ppx after CMV pre-emptive therapy. The median duration of secondary LTV ppx was 127 days (18-270), with no reactivation. LTV was not discontinued due to toxicity or intolerance in any patient. CMV outcomes are summarized in figure 1. All-cause mortality for the 53 pts over the observational period was 11.3%. Conclusion: Primary LTV ppx significantly reduced CMV reactivation, and high-risk patients may benefit from extended prophylaxis. In patients who received preemptive therapy for CMV, use of secondary ppx showed no recurrent CMV reactivation. LTV is well tolerated. Additional studies are needed to determine optimal ppx duration and to clarify role of secondary CMV ppx in high-risk allo-HCT. The future standard of care will likely include extended primary ppx and secondary ppx and result in decreased morbidity and mortality associated with CMV.
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