A pilot study of the CMV inSIGHT T-cell immunity panel to assess cytomegalovirus (CMV) cell mediated immunity (CMI) in allogeneic hematopoietic cell transplant (HCT) recipients.

Abstract

Cytomegalovirus T-cell mediated immunity (CMV CMI) is essential for CMV control after allogeneic hematopoietic cell transplantation (HCT). Clinical experience with commercially available CMV CMI assays in letermovir (LTV) recipients is limited. To evaluate the performance of the CMV inSIGHT T-cell immunity panel (Eurofins Viracor, Lenexa, KS) and factors associated with positive CMV CMI in LTV recipients. We also correlated the CMV inSIGHT with an in-house CMV-induced T-cell activation assay. In this prospective, observational study, the CMV inSIGHT was performed at day (D) 100 post-HCT. Adult recipients of peripheral blood HCT were eligible if they received LTV through D 100. Exclusion criteria included (i) clinically significant (cs) CMV infection by D 100; (ii) acute graft-versus-host disease grade ≥3; and (iii) corticosteroids within 3 weeks prior to CMV CMI testing. Fifty-three adult HCT recipients treated at Memorial Sloan Kettering Cancer Center from May 2020 to December 2024 were enrolled. The primary endpoint was positive CMV CMI at D 100 using the manufacturer's cutoff. The results were not reported to the clinicians. The association between CMV CMI and sub-clinical CMV DNAemia (blips), graft-versus-host disease prophylaxis regimen and lymphocyte subset counts were evaluated in univariate models. Of 53 patients included in the analyzes, 43% received post-transplant cyclophosphamide; and 48% had blips prior to D 100. At D 100, 38 (73%) patients had positive CMV CMI. Blips were associated with positive CMV CMI: odds ratio (OR), (95% confidence interval [95% CI]) 4.89 (1.06-31.73); P = 0.03. Rates of positive CMV CMI were similar between patients on post-transplant cyclophosphamide and calcineurin inhibitors (P = NS). Absolute CD4 and CD8 counts were not correlated with positive CD4 or CD8 CMV CMI respectively. Positive CD4 CMV CMI correlated with positive CD8 CMV CMI; OR (95% CI) 7.16 (1.66-36.41); P = 0.004. Seventy-three percent of letermovir recipients had positive CMV CMI by D 100, indicating CMV-specific immune reconstitution despite letermovir prophylaxis. Interventional studies are needed to assess the utility of the CMV inSIGHT T-cell immunity panel in guiding treatment decisions after discontinuation of letermovir prophylaxis.