127 - Cytomegalovirus DNA “Blips” After Conversion to Letermovir Secondary Prophylaxis in High-Risk Kidney Transplant Recipients

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Author Block: M. Jorgenson¹, J. Descourouez¹, H. Kleiboeker¹, C. Saddler², S. Parajuli², ¹UW Health, Madison, WI, ²University of Wisconsin, Madison, WI
*Purpose: Letermovir (LET) inhibits late-stage cytomegalovirus (CMV) replication, which can lead to non-infectious DNA fragments that can be detected on molecular diagnostics referred to as “blips”. LET blips have been well described in primary prophylaxis, however this phenomenon has not been described in secondary prophylaxis (SP).
*Methods: The study population consisted of adult high risk (CMV D+/R-) kidney transplant recipients receiving LET SP as part of a clinical trial evaluating efficacy of this approach. Study protocol dictates discontinuation of treatment and conversion to LET upon achievement of first viral load (VL) <500 IU/mL. VLs were monitored every 1-2 weeks per study protocol. Primary objective was description of replication trends, resolution and/or failure requiring return to treatment.
*Results: 22 patients met inclusion criteria. The majority were male (81.8%) with lymphocyte depleting induction (63.7%). Mean age was 62.5±8.7 years. Time from transplant to first replication event was 276±104.5 days. Median peak VL on treatment was 18,936 IU/mL (IQR 73,893). Mean duration of CMV-directed treatment prior to SP conversion was 30±10 days. Median VL at conversion to LET SP was 154 IU/mL (range: 0-485 IU/mL, mean 182±164 IU/mL). 77.3% of patients had a VL increase during the 84-day study drug period; 88.2% occurred in the first 2 weeks of SP (Figure 1). Three patients (13.6%) had viral replication that progressed to prophylaxis failure necessitating return to treatment with VGC. This occurred at a mean of 48±2.5 days after starting LET SP. When excluding these patients, median peak VL during successful SP was 313 IU/ml (range: 73-4080 IU/mL, mean 778±1445 IU/mL). Only 3 patients (13.6%) had undetectable replication at LET SP completion.
*Conclusions: VL increases are common during LET SP and typically occur in the first 2 weeks after conversion. While viral replication typically trends down with ongoing LET, theoretically attributable to LET mechanism of action (ie “blips”), replication infrequently completely resolves to negativity during SP. Additionally, clinically significant replication that is attributable to prophylaxis failure can occur. Monitoring VL during LET SP is warranted to capture potential breakthrough and avoid negative outcomes associated with progressive replication.