Bioequivalent Letermovir Usage for Prophylaxis in Haploidentical Stem Cell Transplantation at High Risk of CMV Reactivation: A Report of Two Cases From India

Cytomegalovirus (CMV) reactivation is a major complication in allogeneic hematopoietic stem cell transplantation (HSCT), increasing nonrelapse mortality (NRM) and transplant-related complications. Letermovir, a CMV deoxyribonucleic acid (DNA) terminase inhibitor, has demonstrated efficacy in reducing CMV reactivation without the hematologic toxicity associated with traditional antivirals. We report two HSCT cases, one with a T-cell receptor (TCR) alpha/beta-depleted haploidentical transplant and another haploidentical (6/10 HLA-matched) stem cell transplant, both at significant risk for CMV reactivation. Letermovir prophylaxis was initiated early post-transplant and continued for 100-200 days, depending on risk factors. Both patients remained free of CMV reactivation throughout follow-up (beyond Day +140), with no breakthrough CMV infection or drug-related adverse effects. This case series highlights the first real-world use of letermovir, India's bioequivalent letermovir, in haploidentical transplant recipients, supporting its clinical effectiveness in a resource-limited setting. Real-world outcomes were consistent with previously reported clinical trial data. While outcomes were favorable, the small sample size and single-center experience represent limitations. Nonetheless, the findings highlight the potential benefit of extended prophylaxis beyond Day 100 and the need for individualized CMV prevention strategies in immunosuppressed populations.