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. 2022 Dec 22;10(1):ofac687.
doi: 10.1093/ofid/ofac687. eCollection 2023 Jan.

Real-World Outcomes Associated With Letermovir Use for Cytomegalovirus Primary Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients: A Systematic Review and Meta-analysis of Observational Studies

Ami Vyas  1 , Amit D Raval  2 , Shweta Kamat  1 , Kerry LaPlante  1 , Yuexin Tang  2 , Roy F Chemaly  3
Affiliations

Real-World Outcomes Associated With Letermovir Use for Cytomegalovirus Primary Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients: A Systematic Review and Meta-analysis of Observational Studies

Ami Vyas et al. Open Forum Infect Dis. .

Abstract

Background: A systematic review and meta-analysis of real-world observational studies was conducted to summarize the impact of letermovir cytomegalovirus (CMV) primary prophylaxis (PP) among adult allogeneic hematopoietic cell transplant (allo-HCT) recipients.

Methods: Systematic searches in Medline/PubMed, Embase, and conferences (from database inception to October 2021) were conducted to identify studies for inclusion. Random-effects models were used to derive pooled estimates on the relative effectiveness of letermovir PP compared to controls.

Results: Forty-eight unique studies (N = 7104 patients) were included, most of which were comparative, single-center, and conducted in the United States. Letermovir PP was associated with statistically significant reduction in odds of CMV reactivation (pooled odds ratio [pOR], 0.13 and 0.24; P < .05), clinically significant CMV infection (pOR, 0.09 and 0.19; P < .05), and CMV disease (pOR, 0.31 and 0.35; P < .05) by day +100 and day +200 after allo-HCT, respectively. Letermovir PP was associated with significantly lower odds of all-cause (pOR, 0.73; P < .01) and nonrelapse mortality (pOR, 0.65; P = .01) beyond day 200 after allo-HCT.

Conclusions: Letermovir for CMV PP was effective in reducing the risk of CMV-related complications overall and mortality beyond day 200 among adult allo-HCT recipients.

Keywords: allogeneic hematopoietic cell transplantation; cytomegalovirus; letermovir; meta-analysis.

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Conflict of interest statement

Potential conflicts of interest. A. D. R. was an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, at the time of the conduct of this study, and is a stockholder of Merck & Co., Inc., Rahway, NJ, USA. A. V. received funding from Merck & Co, Inc for performing the analysis. K. L. received investigator-initiated research grants from Merck & Co, Inc, Pfizer, Shionogi, Entasis, National Institutes of Health (NIH), Veteran's Affairs Heath Services Research & Development, and Merits; and served as a consultant for Paratek and Ferring Pharmaceuticals. Y. T. was an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, at the time this study was conducted, and is a stockholder of Merck & Co., Inc., Rahway, NJ, USA. R. F. C. received research grants paid to his institution from the National Cancer Institute, NIH, AiCuris, Ansun Biopharma, Genentech, Chimerix, Janssen, Karius, Merck, Oxford Immunotec, Takeda, and Viracor-Eurofins; and honoraria/consulting fees from Ansun Biopharma, Genentech, Qiagen, Janssen, Merck, Oxford Immunotec, Partner Therapeutics, Pulmotec, Takeda, Shionogi, Adagio, Viracor-Eurofins, and Karius. S. K. reports no potential conflicts.

Figures

Figure 1.
Figure 1.
Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram for study selection. Abbreviations: CMV, cytomegalovirus; RCT, randomized controlled trial.
Figure 2.
Figure 2.
Cytomegalovirus reactivation at D+100 follow-up (A), D+200 follow-up (B), and beyond D+200 follow-up (C). Abbreviations: CI, confidence interval; OR, odds ratio.
Figure 3.
Figure 3.
Clinically significant cytomegalovirus infection at D+100 follow-up (A) and D+200 follow-up (B). Abbreviations: CI, confidence interval; OR, odds ratio.
Figure 4.
Figure 4.
Cytomegalovirus disease at D+100 follow-up (A) and D+200 follow-up (B). Abbreviations: CI, confidence interval; OR, odds ratio.
Figure 5.
Figure 5.
All-cause mortality at D+100 follow-up (A) and beyond D+200 follow-up (B). Abbreviations: CI, confidence interval; OR, odds ratio.
Figure 6.
Figure 6.
Nonrelapse mortality at D+100 follow-up (A) and beyond D+200 follow-up (B). Abbreviations: CI, confidence interval; OR, odds ratio.
See this image and copyright information in PMC

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