TY - JOUR
T1 - Safety and Efficacy of CMX001 as Salvage Therapy for Severe Adenovirus Infections in Immunocompromised Patients
AU - Florescu, Diana F.
AU - Pergam, Steven A.
AU - Neely, Michael N.
AU - Qiu, Fang
AU - Johnston, Christine
AU - Way, Sing Sing
AU - Sande, Jane
AU - Lewinsohn, Deborah A.
AU - Guzman-Cottrill, Judith A.
AU - Graham, Michael L.
AU - Papanicolaou, Genovefa
AU - Kurtzberg, Joanne
AU - Rigdon, Joseph
AU - Painter, Wendy
AU - Mommeja-Marin, Herve
AU - Lanier, Randall
AU - Anderson, Maggie
AU - van der Horst, Charles
N1 - Funding Information:
Financial disclosure: D.F. Florescu: support from Chimerix for travel to collect data for the manuscript; grant from Chimerix for study CMX001-350. S.A. Pergam: consultancy for ViroPharma; grants from ViroPharma, Seattle Genetics, Merck Sharpe & Dohme. M.N. Neely: advisory board Chimerix. F. Qiu: no conflict of interest. C. Johnston: grants from Aicuris GmB & Co. KG and GlaxoSmithKline. S.S. Way: no conflict of interest. J. Sande: no conflict of interest. D.A. Lewinsohn: grant from Chimerix. J.A. Guzman-Cottrill: grant from Chimerix. M.L. Graham: no conflict of interest. G. Papanicolaou: advisory board honorarium from Chimerix. J. Kurtzberg: FACT board member; consultancy: Stemcyte - Scientific Advisor, CORD:USE – Medical Director, NMDP - Medical Advisor; grant from Chimerix. J. Rigdon: no conflict of interest W. Painter: Chimerix employee and stocks. H. Mommeja-Marin: Chimerix employee and stocks. R. Lanier: Chimerix employee and stocks. M. Anderson: Chimerix employee and stocks. C. van der Horst: grants from NIAID (P30-AI-50410), GlaxsoSmithKline.
PY - 2012/5
Y1 - 2012/5
N2 - No therapeutic agent has yet been established as the definitive therapy for adenovirus infections. We describe the clinical experience of 13 immunocompromised patients who received CMX001 (hexadecyloxypropyl cidofovir), an orally bioavailable lipid conjugate of cidofovir, for adenovirus disease. We retrospectively analyzed 13 patients with adenovirus disease and viremia treated with CMX001; data were available for ≥4 weeks after initiation of CMX001 therapy. Virologic response (VR) was defined as a 99% drop from baseline or undetectable adenovirus DNA in serum. The median age of the group was 6 years (range, 0.92-66 years). One patient had severe combined immunodeficiency, 1 patient was a small bowel transplant recipient, and 11 were allogeneic stem cell transplant recipients. Adenovirus disease was diagnosed at a median of 75 days (range, 15-720 days) after transplantation. All patients received i.v. cidofovir for a median of 21 days (range, 5-90 days) before CMX001 therapy. The median absolute lymphocyte count at CMX001 initiation was 300 cells/μL (range, 7-1500 cells/μL). Eight patients (61.5%) had a ≥1 log10 drop in viral load after the first week of therapy. By week 8, 9 patients (69.2%) demonstrated a VR, with a median time to achieve VR of 7 days (range, 3-35 days). The change in absolute lymphocyte count was inversely correlated with the change in log10 viral load only at week 6 (r = -0.74; P = .03). Patients with VR had longer survival than those without VR (median 196 days versus 54.5 days; P = .04). No serious adverse events were attributed to CMX001 during therapy. CMX001 may be a promising therapeutic option for the treatment of severe adenovirus disease in immunocompromised patients.
AB - No therapeutic agent has yet been established as the definitive therapy for adenovirus infections. We describe the clinical experience of 13 immunocompromised patients who received CMX001 (hexadecyloxypropyl cidofovir), an orally bioavailable lipid conjugate of cidofovir, for adenovirus disease. We retrospectively analyzed 13 patients with adenovirus disease and viremia treated with CMX001; data were available for ≥4 weeks after initiation of CMX001 therapy. Virologic response (VR) was defined as a 99% drop from baseline or undetectable adenovirus DNA in serum. The median age of the group was 6 years (range, 0.92-66 years). One patient had severe combined immunodeficiency, 1 patient was a small bowel transplant recipient, and 11 were allogeneic stem cell transplant recipients. Adenovirus disease was diagnosed at a median of 75 days (range, 15-720 days) after transplantation. All patients received i.v. cidofovir for a median of 21 days (range, 5-90 days) before CMX001 therapy. The median absolute lymphocyte count at CMX001 initiation was 300 cells/μL (range, 7-1500 cells/μL). Eight patients (61.5%) had a ≥1 log10 drop in viral load after the first week of therapy. By week 8, 9 patients (69.2%) demonstrated a VR, with a median time to achieve VR of 7 days (range, 3-35 days). The change in absolute lymphocyte count was inversely correlated with the change in log10 viral load only at week 6 (r = -0.74; P = .03). Patients with VR had longer survival than those without VR (median 196 days versus 54.5 days; P = .04). No serious adverse events were attributed to CMX001 during therapy. CMX001 may be a promising therapeutic option for the treatment of severe adenovirus disease in immunocompromised patients.
KW - Allogeneic stem cell transplant
KW - Nephrotoxicity
KW - Small bowel transplant
KW - Therapeutic option
KW - Treatment
KW - Virologic response
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UR - http://www.scopus.com/inward/citedby.url?scp=84859872029&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2011.09.007
DO - 10.1016/j.bbmt.2011.09.007
M3 - Article
C2 - 21963623
AN - SCOPUS:84859872029
SN - 1083-8791
VL - 18
SP - 731
EP - 738
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 5
ER -