Safety and Efficacy of CMX001 as Salvage Therapy for Severe Adenovirus Infections in Immunocompromised Patients

Diana F. Florescu, Steven A. Pergam, Michael N. Neely, Fang Qiu, Christine Johnston, Sing Sing Way, Jane Sande, Deborah A. Lewinsohn, Judith A. Guzman-Cottrill, Michael L. Graham, Genovefa Papanicolaou, Joanne Kurtzberg, Joseph Rigdon, Wendy Painter, Herve Mommeja-Marin, Randall Lanier, Maggie Anderson, Charles van der Horst

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)731-738
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume18
Issue number5
DOIs
StatePublished - May 1 2012

Keywords

  • Allogeneic stem cell transplant
  • Nephrotoxicity
  • Small bowel transplant
  • Therapeutic option
  • Treatment
  • Virologic response

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Florescu, D. F., Pergam, S. A., Neely, M. N., Qiu, F., Johnston, C., Way, S. S., Sande, J., Lewinsohn, D. A., Guzman-Cottrill, J. A., Graham, M. L., Papanicolaou, G., Kurtzberg, J., Rigdon, J., Painter, W., Mommeja-Marin, H., Lanier, R., Anderson, M., & van der Horst, C. (2012). Safety and Efficacy of CMX001 as Salvage Therapy for Severe Adenovirus Infections in Immunocompromised Patients. Biology of Blood and Marrow Transplantation, 18(5), 731-738. https://doi.org/10.1016/j.bbmt.2011.09.007