Letermovir for prevention of cytomegalovirus reactivation in haploidentical and mismatched adult donor allogeneic hematopoietic cell transplantation with post-transplant cyclophosphamide for graft-versus-host disease prophylaxis

Biol Blood Marrow Transplant. 2020 Oct 11:S1083-8791(20)30663-7. doi: 10.1016/j.bbmt.2020.10.009. Online ahead of print.


Cytomegalovirus (CMV) is serious viral infection in allogeneic hematopoietic cell transplantation (allo HCT) recipients. November 2017, the novel CMV DNA terminase complex inhibitor letermovir was approved for prophylaxis of CMV infection in CMV-seropositive allo HCT recipients. Here, we sought to determine the effectiveness of letermovir in preventing CMV infection in CMV-seropositive patients undergoing haploidentical or mismatched adult unrelated donor allo HCT using post-transplant cyclophosphamide-based graft-versus host-disease prophylaxis. Sixty-four patients were transplanted between 2014 and 2019 of whom 32 received letermovir and 32 did not receive letermovir. The day 180 cumulative incidence of CMV infection requiring therapy was 45.3% (95% conf. interval 32.7% - 57.1%) in the entire cohort, 68.8% (48.9% - 82.2%) in the patients that did not receive letermovir, and 21.9% (9.5% - 37.6%, P < 0.001) in patients that received letermovir. Adjusting for regimen intensity, disease histology, and age, the hazard ratio for CMV infection was 0.19 (0.08 - 0.47, P < 0.001) in patients that received primary prophylaxis with letermovir. The one-year cumulative incidence of treatment related mortality was similar between patients with and without letermovir treatment (16.9% versus 18.9%) as was overall survival (64.0% versus 49.0%, respectively). Persistent CMV infection requiring >28 days of therapy was more common in patients that did not receive letermovir (31.2% versus 6.2%, P = 0.02). In summary, letermovir was effective at preventing CMV infection in this high-risk population of HLA mismatched allo HCT recipients.

PMID:33053449 | DOI:10.1016/j.bbmt.2020.10.009