Yoshiki Hayashi, Yoshinobu Kanda, Hirohisa Nakamae, Masatsugu Tanaka, Noriko Doki, Michihiro Hidaka, Shingo Yano, Kazuo Hatanaka, Akio Kohno, Yukiyoshi Moriuchi, Toshio Wakayama, Takuya Yamashita, Tohru Takata, Minoru Yoshida, Masayuki Hino, Takuhiro Yamaguchi, Takahiro Fukuda
Graft-versus-host disease (GVHD) increases the risk of invasive fungal infection (IFI) after allogeneic hematopoietic cell transplantation (HCT). This randomized phase II selection trial evaluated protocol-defined prophylaxis success and safety of voriconazole (VRCZ) and itraconazole (ITCZ) prophylaxis in patients with GVHD.Allogeneic HCT recipients with grade II-IV acute GVHD or chronic GVHD requiring systemic corticosteroids were randomized to receive VRCZ or ITCZ for 60 days. Success was defined as survival without protocol-defined proven/probable IFI through day 60 and receipt of study drug for at least 48 days.Sixty-six patients (33 per group) were randomized. The success rate was 88% with VRCZ and 94% with ITCZ (difference, - 6.1 percentage points; 95% confidence interval, - 20.0 to 7.7); ITCZ was selected by the prespecified rule. No protocol-defined IFI occurred with VRCZ; one probable and one possible IFI occurred with ITCZ. Post hoc reclassification using 2008 consensus criteria yielded no IFI, whereas 2020 updated criteria yielded possible IFI in one VRCZ and two ITCZ patients. Grade 3/4 adverse events occurred in 27% and 21%, respectively.In conclusion, both regimens achieved high protocol-defined prophylaxis success. The study was not powered to establish comparative antifungal efficacy; results mainly inform feasibility of azole prophylaxis in GVHD.