Systematic review and meta-analysis of real-world observational studies provide additional evidence of effectiveness of Prevymis in preventing cytomegalovirus infection and disease in adults undergoing allogeneic HCT.

In the analysis of 48 real-world observational studies, compared to controls (mostly preemptive therapy), primary prophylaxis with Prevymis was associated at 100 days of follow-up after alloHCT with: 87% lower odds of CMV reactivation (N=3,054 across 18 studies; Pooled Odds Ratio (POR)=0.13, [95% CI, 0.08, 0.22]); 91% lower odds for clinically significant CMV infection (N=3,993 across 21 studies; POR=0.09, [95% CI, 0.05, 0.14]); 69% lower odds of CMV disease (N=1,838 across 10 studies; POR=0.31, [95% CI, 0.12, 0.77]); 94% lower odds of CMV-related hospitalization (N=905 across 2 studies; POR=0.06, [95% CI, 0.01, 0.28]); and 48% lower odds of Grade 2 or greater graft versus host disease (GvHD) (N=471 across 6 studies; POR=0.52, [95% CI, 0.32, 0.86]). Consistent results were observed at 200 days of follow-up with respect to CMV reactivation, clinically significant CMV infection, and CMV disease. The findings were presented during an oral session at the European Society for Blood and Marrow Transplantation (EBMT) 48th Annual Meeting (Abstract #OS04-07).

Patients undergoing alloHCT(allogeneic hematopoietic cell transplantation) who are CMV-seropositive [R+] are at high risk for CMV reactivation. CMV infection is a common clinically significant complication in these patients and early CMV reactivation after alloHCT is associated with increased mortality. Prevymis is a first-in-class antiviral agent that was approved by the FDA in 2017 and is indicated for prophylaxis of CMV infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT).

Real-World Outcomes for Primary Prophylaxis of CMV Infection and Disease Using Prevymis: The objective of the analysis was to assess the effectiveness of primary prophylaxis with Prevymis among adults undergoing alloHCT using systematic literature review and meta-analysis of data from real-world observational studies. An initial search of peer-reviewed publications via PubMed and Embase and relevant conference proceedings through October 2021 identified 576 records. Further screening to identify publications that met the pre-specified inclusion criteria yielded 48 distinct studies (22 full publications and 26 conference proceedings) that reported on outcomes of Prevymis for primary prophylaxis in patients undergoing alloHCT. These studies involved patients predominantly in the United States, Italy, and Japan and employed a range of timepoints for initiation of PREVYMIS post-transplant (0 - 42 days) and duration of therapy (79 - 191 days). Forty of the 48 studies were comparator studies and, in all but one study, the control was preemptive therapy; the other eight studies were single-arm studies.

Outcomes measured included CMV reactivation, clinically significant CMV infection, CMV disease, CMV-related hospitalizations, time to CMV viremia (infection detected in the blood), graft versus host disease (GvHD) (Grade 2 or greater), and all-cause and non-relapse mortality. In addition to the results discussed above, primary prophylaxis with Prevymis was also associated in this meta-analysis with the following outcomes compared to controls: At 100 days of follow-up after alloHCT: i. 30% lower odds of all-cause mortality (N=1,723 across 5 studies; POR=0.70, [95% CI, 0.46, 1.07]). ii. 30% lower odds of non-relapse mortality (N=889 across 3 studies; POR=0.70, [95% CI, 0.39, 1.25]) At 200 days of follow-up after alloHCT: i. 76% lower odds of CMV reactivation (N=1,297 across 5 studies; POR=0.24, [95% CI, 0.18, 0.32]). ii. 81% lower odds for clinically significant CMV infection (N=2,771 across 14 studies; POR=0.19, [95% CI, 0.14, 0.25]).iii. 65% lower odds of CMV disease (N=1,261 across 7 studies; POR=0.35, [95% CI, 0.16, 0.78]). At more than 200 days of follow-up after alloHCT: i. 78% lower odds of CMV reactivation (N=2,109 across 8 studies; POR=0.22, [95% CI, 0.15, 0.32]). ii. 27% lower odds for all-cause mortality (N=2,685 across 15 studies; POR=0.73, [95% CI, 0.60, 0.90]) iii. 35% lower odds for non-relapse mortality (N=1,829 across 6 studies; POR=0.65, [95% CI, 0.47, 0.90]).

Selected Safety Information about Prevymis (letermovir): Prevymis is contraindicated in patients receiving pimozide or ergot alkaloids. Increased pimozide concentrations may lead to QT prolongation and torsades de pointes. Increased ergot alkaloids concentrations may lead to ergotism. Prevymis is contraindicated with pitavastatin and simvastatin when co-administered with cyclosporine. Significantly increased pitavastatin or simvastatin concentrations may lead to myopathy or rhabdomyolysis. The concomitant use of Prevymis and certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions (Prevymis or concomitant drugs) or reduced therapeutic effect of Prevymis or the concomitant drug. Consider the potential for drug interactions prior to and during Prevymis therapy; review concomitant medications during Prevymis therapy; and monitor for adverse reactions associated with Prevymis and concomitant medications. The cardiac adverse event rate (regardless of investigator-assessed causality) was higher in subjects receiving Prevymis than placebo (13% vs 6%). The most common cardiac adverse events were tachycardia (reported in 4% Prevymis subjects and 2% placebo subjects) and atrial fibrillation (reported in 3% Prevymis subjects and 1% placebo subjects). Among those subjects who experienced one or more cardiac adverse events, 85% of Prevymis and 92% of placebo subjects had events reported as mild or moderate in severity.