Preventing cytomegalovirus in high-risk haploidentical hematopoietic stem cell transplant: A dual case comparison of letermovir prophylaxis versus no prophylaxis

INTRODUCTION

The risk of cytomegalovirus (CMV) reactivation after transplant can range from 30% to 70%, depending on several factors, such as the type of transplant, immune-suppressive drugs, delayed immune reconstitution, and serology status of donor or recipient before transplant.^[1-4] While treatment with ganciclovir and foscarnet is effective but can cause significant myelosuppression and nephrotoxicity.^[5] Letermovir target CMV DNA terminase complex (UL56 gene) without myelotoxicity and nephrotoxicity.^[6,7] Phase 3 trial demonstrated significant activity of letermovir in reducing CMV infection rates, leading to the Food and Drug Administration approval in 2017.^[8,9]

In Low-and-Middle-Income Countries like India, financial constraints often dictate the choice between a “prophylaxis” strategy and a “pre-emptive strategy.” The cost of letermovir is not covered in any of the government health schemes available for the medical treatment.

This report highlights the real-world efficacy of letermovir by comparing two patients with identical conditions and regimes but different approaches.^[10-13]

CASE REPORT

DISCUSSION

CMV reactivation rate is high due to delayed immune reconstitution following haploidentical HSCT.^[1,4] Patient 1 received letermovir as preventive treatment and stayed CMV-negative, while Patient 2 did not receive the drug and developed CMV reactivation [Table 1]. These outcomes are consistent with major studies demonstrating the efficacy of letermovir without significant myelotoxicity and nephrotoxicity.^[8,9,12]

In our case, Patient 1 safely received letermovir alongside MMF and tacrolimus consistent with previous studies.^[7,14]

Extended prophylaxis beyond 100 days may further reduce CMV reactivation.^[15-17]

Although letermovir is more expensive up front, it is more cost-effective by reducing hospital stays, diagnostic tests, and use of second-line treatments.^[16] The first patient’s case shows that the drug is becoming more adopted in India, supported by studies confirming the safety and affordability of locally made bioequivalent versions.^[10] However, still cost remains a major barrier as illustrated by our second patient who could not receive prophylaxis because of financial constraints.

Finally, as George et al. emphasized, CMV risk depends not only on the virus itself but also on patient-specific factors such as age, GVHD, and immune recovery. In our case, Patient 2’s older age and suspected GVHD likely worsened the outcome.^[18]

CONCLUSION

In high-risk haploidentical HSCT settings, delayed immune reconstitution significantly elevates the risk of CMV reactivation and associated non-relapse mortality. These cases demonstrate that letermovir prophylaxis effectively prevents reactivation without added toxicities. While the letermovir has the potential to reduce overall healthcare costs by preventing complications, high acquisition costs remain a major barrier. Consequently, for high-risk patients – particularly those with advanced age or GVHD – letermovir prophylaxis should no longer be viewed as an elective intervention but rather established as the primary standard of care. Facilitating its inclusion in government health schemes is critical to overcoming financial barriers and optimizing post-transplant outcomes in resource-limited settings.