Letermovir Prophylaxis for Cytomegalovirus Infection in Adult Allogeneic Stem Cell Transplantation: A Retrospective Analysis From a Lower-Middle-Income Country

TL;DR

This study compares the effectiveness of two versions of letermovir in preventing CMV infection in stem cell transplant patients in India.

Contribution

The study provides the first real-world data comparing innovator and bioequivalent letermovir in a lower-middle-income country.

Findings

CMV reactivation occurred in 20.7% of patients, with no significant difference between drug versions.

Bioequivalent letermovir was as effective and safe as the innovator formulation.

Cost-effective access to letermovir may improve transplant outcomes in resource-limited settings.

Abstract

Background: Cytomegalovirus (CMV) reactivation remains a leading cause of morbidity and non-relapse mortality following allogeneic hematopoietic stem cell transplantation (HSCT), especially in high-seroprevalence, resource-limited settings. Letermovir has significantly improved CMV prophylaxis by providing effective antiviral protection without hematologic or renal toxicity. The present study provides the first real-world comparative data of innovator and bioequivalent letermovir formulations for CMV prophylaxis in adult allogenic HSCT recipients from India.

Methods: This retrospective study was conducted at the Adult Hematology and Bone Marrow Transplant Unit, Fortis Memorial Research Institute, Gurugram, India. It included 29 CMV-seropositive patients’ data of allogeneic HSCT recipients who received letermovir prophylaxis from day +7 to day +100 (innovator n = 7; bioequivalent n = 22). Treatment allocation was based on institutional availability and consultant discretion, with baseline characteristics comparable in both groups. Weekly quantitative CMV PCR monitoring was performed during prophylaxis, with continued surveillance thereafter as per institutional practice. The primary endpoint was CMV-free survival through day +100. Secondary endpoints included CMV reactivation incidence, time to CMV breakthrough, and overall survival. Statistical analyses were performed using IBM SPSS Statistics for Windows version 25.0, with p < 0.05 considered significant.

Results: The mean recipient age in the analysed data was 34.1 ± 13.2 years, with 82.8% males; 62% patients that underwent haploidentical transplants. CMV reactivation data showed occurrence in six patients (20.7%) overall, four (13.8%) in the bioequivalent group, and two (28.6%) in the innovator group (p = 0.56). Two patients in the bioequivalent group developed CMV reactivation after completion of prophylaxis at days 121 and 130, respectively. The overall median duration to CMV breakthrough was 121 days as observed (121 vs. 84 days; log-rank = 1.88; p = 0.17).

Conclusion: No statistically significant differences were observed between innovator and bioequivalent letermovir formulations with respect to safety or CMV outcomes. Availability of a cost-effective bioequivalent formulation may substantially expand access to CMV prophylaxis, supporting improved transplant outcomes in high-burden LMICs.

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