Maribavir for Refractory Cytomegalovirus Infections With or Without Resistance Post-Transplant: Results From a Phase 3 Randomized Clinical Trial.

Journal Article (Clinical Trial, Phase III;Journal Article)

BACKGROUND: Therapies for refractory cytomegalovirus infections (with or without resistance [R/R]) in transplant recipients are limited by toxicities. Maribavir has multimodal anti-cytomegalovirus activity through the inhibition of UL97 protein kinase. METHODS: In this phase 3, open-label study, hematopoietic-cell and solid-organ transplant recipients with R/R cytomegalovirus were randomized 2:1 to maribavir 400 mg twice daily or investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for 8 weeks, with 12 weeks of follow-up. The primary endpoint was confirmed cytomegalovirus clearance at end of week 8. The key secondary endpoint was achievement of cytomegalovirus clearance and symptom control at end of week 8, maintained through week 16. RESULTS: 352 patients were randomized (235 maribavir; 117 IAT). Significantly more patients in the maribavir versus IAT group achieved the primary endpoint (55.7% vs 23.9%; adjusted difference [95% confidence interval (CI)]: 32.8% [22.80-42.74]; Pā€…<ā€….001) and key secondary endpoint (18.7% vs 10.3%; adjusted difference [95% CI]: 9.5% [2.02-16.88]; Pā€…=ā€….01). Rates of treatment-emergent adverse events (TEAEs) were similar between groups (maribavir, 97.4%; IAT, 91.4%). Maribavir was associated with less acute kidney injury versus foscarnet (8.5% vs 21.3%) and neutropenia versus valganciclovir/ganciclovir (9.4% vs 33.9%). Fewer patients discontinued treatment due to TEAEs with maribavir (13.2%) than IAT (31.9%). One patient per group had fatal treatment-related TEAEs. CONCLUSIONS: Maribavir was superior to IAT for cytomegalovirus viremia clearance and viremia clearance plus symptom control maintained post-therapy in transplant recipients with R/R cytomegalovirus. Maribavir had fewer treatment discontinuations due to TEAEs than IAT. Clinical Trials Registration. NCT02931539 (SOLSTICE).

Full Text

Duke Authors

Cited Authors

  • Avery, RK; Alain, S; Alexander, BD; Blumberg, EA; Chemaly, RF; Cordonnier, C; Duarte, RF; Florescu, DF; Kamar, N; Kumar, D; Maertens, J; Marty, FM; Papanicolaou, GA; Silveira, FP; Witzke, O; Wu, J; Sundberg, AK; Fournier, M; SOLSTICE Trial Investigators,

Published Date

  • September 10, 2022

Published In

Volume / Issue

  • 75 / 4

Start / End Page

  • 690 - 701

PubMed ID

  • 34864943

Pubmed Central ID

  • PMC9464078

Electronic International Standard Serial Number (EISSN)

  • 1537-6591

Digital Object Identifier (DOI)

  • 10.1093/cid/ciab988

Language

  • eng

Conference Location

  • United States