Letermovir Effective for Allogeneic Hematopoietic Stem Cell Transplant Recipients

Letermovir was effective as primary prophylaxis against cytomegalovirus reactivation in allogeneic hematopoietic cell transplant recipients.

Letermovir as primary prophylaxis against cytomegalovirus (CMV) infection in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients is effective and reduces the risk of mortality and reducing CMV-related complications. These study results were published in Open Forum Infectious Diseases.

In this international meta-analysis and systematic review of real-world observational studies, researchers evaluated CMV outcomes and all-cause mortality risk among allo-HSCT recipients following the use of letermovir as primary prophylaxis against CMV infection. Pooled estimates on the relative effectiveness of letermovir were compared between intervention and control patients via random-effects models.

The analysis comprised 48 unique studies. The number of patients in the letermovir (median age range, 42-65 years) and control (median age range, 26-65 years) groups among the included studies ranged between 12 and 204 and 18 and 637, respectively.

In the pooled analysis, patients who received letermovir had a significantly reduced risk for CMV reactivation at days 100 (odds ratio [OR], 0.13; 95% CI, 0.08-0.22; I2 =74%)and200 (OR, 0.24; 95% CI, 0.18-0.32) after transplantation compared with those in the control group. Further between-group analysis showed letermovir prophylaxis also reduced the risk for clinically significant CMV infection at both 100 (OR, 0.09; 95% CI, 0.05-0.14; I2 =76%) and 200 days (OR, 0.19; 95% CI, 0.14-0.25; I2 =47%).

‘[L]etermovir PP may reduce, shorten duration, or delay PET with antiviral agents that are associated with serious toxicities,’ the researchers noted.

At day 100 following transplantation, the risk of all-cause mortality was significantly decreased among patients in the letermovir vs control groups (OR, 0.73; 95% CI, 0.36-1.07; P <.01). Similar findings were observed among patients in the letermovir group in regard to the risk of nonrelapse-related mortality at day 100 (OR, 0.70; P =.23). Letermovir also was associated with reduced risk for CMV-related hospitalization at day 100 (OR, 0.08; 95% CI, 0.02-0.36; P <0.01).

Limitations of this analysis were the small sample sizes and short follow-up periods among the included studies.

“[L]etermovir PP [primary prophylaxis] may reduce, shorten duration, or delay PET [preemptive therapy] with antiviral agents that are associated with serious toxicities,” the researchers noted.

Disclosure: Disclosure: This research was supported by Merck & Co., Inc. Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References:

Vyas A, Raval AD, Kamat S, LaPlante K, Tang Y, Chemaly RF. 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. Open Infect Dis. Published online December 22, 2022. doi:10.1093/ofid/ofac687