학술논문
A phase III randomized crossover trial of plerixafor versus G-CSF for treatment of WHIM syndrome.
Document Type
Article
Author
McDermott, David H.; Velez, Daniel; Elena Cho; Cowen, Edward W.; DiGiovanna, John J.; Pastrana, Diana V.; Buck, Christopher B.; Calvo, Katherine R.; Gardner, Pamela J.; Rosenzweig, Sergio D.; Stratton, Pamela; Merideth, Melissa A.; Kim, H. Jeffrey; Brewer, Carmen; Katz, James D.; Kuhns, Douglas B.; Malech, Harry L.; Follmann, Dean; Fay, Michael P.; Murphy, Philip M.
Source
Subject
*LYMPHOPENIA
*CROSSOVER trials
*WARTS
*CLINICAL trials
*PRIMARY immunodeficiency diseases
*SYNDROMES
*GAIN-of-function mutations
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Language
ISSN
0021-9738
Abstract
BACKGROUND. Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a primary immunodeficiency disorder caused by heterozygous gain-of-function CXCR4 mutations. Myelokathexis is a kind of neutropenia caused by neutrophil retention in bone marrow and in WHIM syndrome is associated with lymphopenia and monocytopenia. The CXCR4 antagonist plerixafor mobilizes leukocytes to the blood; however, its safety and efficacy in WHIM syndrome are undefined. METHODS. In this investigator-initiated, single-center, quadruple-masked phase III crossover trial, we compared the total infection severity score (TISS) as the primary endpoint in an intent-to-treat manner in 19 patients with WHIM who each received 12 months treatment with plerixafor and 12 months treatment with granulocyte CSF (G-CSF, the standard of care for severe congenital neutropenia). The treatment order was randomized for each patient. RESULTS. Plerixafor was nonsuperior to G-CSF for TISS (P = 0.54). In exploratory endpoints, plerixafor was noninferior to G-CSF for maintaining neutrophil counts of more than 500 cells/μL (P = 0.023) and was superior to G-CSF for maintaining lymphocyte counts above 1,000 cells/μL (P < 0.0001). Complete regression of a subset of large wart areas occurred on plerixafor in 5 of 7 patients with major wart burdens at baseline. Transient rash occurred on plerixafor, and bone pain was more common on G-CSF. There were no significant differences in drug preference or quality of life or the incidence of drug failure or serious adverse events. CONCLUSION. Plerixafor was not superior to G-CSF in patients with WHIM for TISS, the primary endpoint. Together with wart regression and hematologic improvement, the infection severity results support continued study of plerixafor as a potential treatment for WHIM syndrome. [ABSTRACT FROM AUTHOR]