Table 2.
Letermovir primary prophylaxis: summary of clinical studies in hematopoietic cell transplant.
| Study design | No. of patients | Outcomes | |
|---|---|---|---|
| Clinical trials | |||
| Chemaly et al.17 | Phase IIb Prospective, randomized, placebo controlled, multi-center, dose ranging |
LTV (60 mg), n = 33 LTV (120 mg), n = 31 LTV (240 mg), n = 34 Placebo, n = 33 |
All-cause prophylaxis failure,-no. (%); p value LTV versus placebo LTV (60 mg) = 16 (48%), p = 0.32 LTV (120 mg) = 10 (32%), p = 0.01 LTV (240 mg) = 10 (29%), p = 0.007 Placebo = 21 (64%) Any drug-related adverse event, no. (%) LTV (60 mg) = 11 (33%) LTV (120 mg) = 4 (13%) LTV (240 mg) = 2 (6%) Placebo = 11 (33%) |
| Marty et al.16 | Phase III Prospective, randomized, placebo controlled, multi-center |
LTV, n = 325 Placebo, n = 170 |
CS-CMVi at week 14,-no. (%) LTV 62 (19.1%) versus 85 (50%), p < 0.001 CS-CMVi at week 24,-no. (%) LTV = 122 (37.5%) versus placebo = 103 (60.6%), p < 0.001 All-cause mortality at week 24 LTV = 10.2% versus placebo = 15.9%, p = 0.03 All-cause mortality at week 48 LTV = 20.9% versus placebo = 25.5%, p = 0.12 Any adverse event (LTV n = 373, placebo n = 192), no. (%) LTV = 365 (97.9% versus placebo = 192 (100%), p = 0.07 |
| Phase III follow-up analyses | |||
| Marty et al.18 | Analysis of patients with detectable CMV at randomization excluded from phase III trial | LTV, n = 48 Placebo, n = 22 |
CS-CMVi at week 14,-no. (%) LTV = 22 (45.8%) versus placebo = 20 (90.9%), p < 0.001 CS-CMVi at week 24,-no. (%) LTV = 31 (64.6%) versus placebo = 20 (90.9%), p < 0.01 All-cause mortality at week 24 LTV = 15% versus placebo = 18.2%, no reported p value All-cause mortality at week 48 LTV = 26.5% versus placebo = 40.9%, p = 0.268 |
| Ljungman et al.19 | Post hoc analysis of phase III data | Week 24 (59 deaths) LTV, n = 293 Placebo, n = 143 Week 48 (101 deaths) LTV, n = 264 Placebo, n = 130 |
HR all-cause mortality at week 24 (LTV versus placebo) 0.58 (95% CI, 0.35–0.98), p = 0.04 HR all-cause mortality at week 48 (LTV versus placebo) 0.74 (95% CI, 0.49–1.11), p = 0.14 HR of letermovir group with versus without CS-CMVi (week 48) 1.15 (95% CI, 0.56–2.37), p = 0.71 HR of placebo group with versus without CS-CMVi (week 48) 2.34 (95% CI, 1.17–4.67), p = 0.02 HR all-cause mortality CS-CMVi (LTV versus placebo) 0.45 (95% CI, 0.21–1.00), p = 0.05 |
CS-CMVi, clinically significant CMV infection; LTV, letermovir.