Date: Monday, June 13, 2016
Session Time: 4:30pm-6:00pm
Presentation Time: 4:54pm-5:06pm
Location: Room 306
Patients treated for CMV viremia commonly relapse after discontinuation of therapy. CMV-specific CD8+ T-cell mediated immunity (CMI) is useful to predict the risk of CMV reactivation but has not been evaluated in interventional trials. We hypothesized that CMI assessment could be used to tailor therapy for CMV viremia by guiding the need for secondary prophylaxis following initial treatment.
Transplant patients were enrolled in this prospective study at the onset of CMV viremia requiring antiviral therapy (>1000 IU/mL). CMI was measured serially using the Quantiferon-CMV (QFT-CMV) assay. Patients were treated with antiviral therapy until viral load was negative. Following that, the real-time result of the QFT-CMV assay was used to guide therapy: patients with a positive CMI assay had antivirals discontinued; patients with a negative CMI had two months of secondary antiviral prophylaxis. All patients were monitored by serial CMV PCR assays. The primary endpoint was relapse defined as detectable viremia (>137 IU/ml) requiring antiviral therapy.
We enrolled 21 patients (liver=4, lung=7, kidney=6, combined=4) of which 17 had sufficient follow-up for analysis. Median age was 53 years (range 29-76) and 10 patients had symptomatic CMV disease and 7 patients had asymptomatic viremia. Median viral load at onset was 10,900 IU/ml (range 1,920-1,220,000). All patients received antiviral therapy until viral load was negative. Relapse occurred in 9 patients (52.9%) at a median of 59 days (range 7-169). At end-of-treatment, 6 patients (35.3%) had a positive CMI response (median IFN-γ response to CMV=3.40 IU/mL) and discontinued antivirals. CMI was negative in 11 patients (64.7%), who therefore received 2 months of secondary prophylaxis. During the follow-up, patients with a negative CMI were still more likely to have CMV relapse compared with those who were positive [8/11 (72.7%) vs. 1/6 (16.7%), p=0.05). Hospitalization due to CMV disease tended to be lower in the CMI positive vs. CMI negative patients (0/6 (0%) vs. 5/11 (45.5%); p=0.1).
This study provides a first proof of concept that therapy for CMV viremia can be successfully tailored based on measurement of the CMV specific CD8+ T-cell response. This allowed minimization of antivirals in a subset of patients without adverse sequelae.
CITATION INFORMATION: Mian M, Humar A, Keshwani S, Husain S, Ashton P, Han S, Singer L, Kim J, Renner E, Kumar D. An Interventional Study Evaluating Cell Mediated Immunity to Guide Therapy for CMV Viremia. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Mian M, Humar A, Keshwani S, Husain S, Ashton P, Han S, Singer L, Kim J, Renner E, Kumar D. An Interventional Study Evaluating Cell Mediated Immunity to Guide Therapy for CMV Viremia. [abstract]. Am J Transplant. 2016; 16 (suppl 3). http://atcmeetingabstracts.com/abstract/an-interventional-study-evaluating-cell-mediated-immunity-to-guide-therapy-for-cmv-viremia/. Accessed December 18, 2017.
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