%0 Journal Article
%T A phase 3 randomized trial of mavorixafor, a CXCR4 antagonist, for WHIM syndrome.
%A Badolato R
%A Alsina L
%A Azar A
%A Bertrand Y
%A Bolyard AA
%A Dale D
%A Deyà-Martínez À
%A Dickerson KE
%A Ezra N
%A Hasle H
%A Kang HJ
%A Kiani-Alikhan S
%A Kuijpers TW
%A Kulagin A
%A Langguth D
%A Levin C
%A Neth O
%A Olbrich P
%A Peake J
%A Rodina Y
%A Rutten CE
%A Shcherbina A
%A Tarrant TK
%A Vossen MG
%A Wysocki CA
%A Belschner A
%A Bridger GJ
%A Chen K
%A Dubuc S
%A Hu Y
%A Jiang H
%A Li S
%A MacLeod R
%A Stewart M
%A Taveras AG
%A Yan T
%A Donadieu J
%J Blood
%V 144
%N 1
%D 2024 Jul 4
%M 38643510
%F 25.476
%R 10.1182/blood.2023022658
%X <B>UNASSIGNED: </B>We investigated efficacy and safety of mavorixafor, an oral CXCR4 antagonist, in participants with warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a rare immunodeficiency caused by CXCR4 gain-of-function variants. This randomized (1:1), double-blind, placebo-controlled, phase 3 trial enrolled participants aged ≥12 years with WHIM syndrome and absolute neutrophil count (ANC) ≤0.4 × 103/μL. Participants received once-daily mavorixafor or placebo for 52 weeks. The primary end point was time (hours) above ANC threshold ≥0.5 × 103/μL (TATANC; over 24 hours). Secondary end points included TAT absolute lymphocyte count ≥1.0 × 103/μL (TATALC; over 24 hours); absolute changes in white blood cell (WBC), ANC, and absolute lymphocyte count (ALC) from baseline; annualized infection rate; infection duration; and total infection score (combined infection number/severity). In 31 participants (mavorixafor, n = 14; placebo, n = 17), mavorixafor least squares (LS) mean TATANC was 15.0 hours and 2.8 hours for placebo (P < .001). Mavorixafor LS mean TATALC was 15.8 hours and 4.6 hours for placebo (P < .001). Annualized infection rates were 60% lower with mavorixafor vs placebo (LS mean 1.7 vs 4.2; nominal P = .007), and total infection scores were 40% lower (7.4 [95% confidence interval [CI], 1.6-13.2] vs 12.3 [95% CI, 7.2-17.3]). Treatment with mavorixafor reduced infection frequency, severity, duration, and antibiotic use. No discontinuations occurred due to treatment-emergent adverse events (TEAEs); no related serious TEAEs were observed. Overall, mavorixafor treatment demonstrated significant increases in LS mean TATANC and TATALC, reduced infection frequency, severity/duration, and was well tolerated. The trial was registered at www.clinicaltrials.gov as #NCT03995108.