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Cytomegalovirus (CMV) Reactivation and CMV-Specific Cell-Mediated Immunity After Chimeric Antigen Receptor T-Cell
Eleftheria Kampouri1, Sarah S Ibrahimi1, Hu Xie2
1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Insights
Cytomegalovirus (CMV) reactivation occurs in 25% of patients after chimeric antigen receptor T-cell therapy (CARTx). BCMA-targeted CARTx and corticosteroid use increase CMV reactivation risk, suggesting targeted surveillance.
Area of Science:
- Immunology
- Oncology
- Infectious Diseases
Background:
- Cytomegalovirus (CMV) epidemiology post-chimeric antigen receptor T-cell therapy (CARTx) is understudied due to limited surveillance.
- Understanding CMV incidence and risk factors after CARTx is crucial for patient management.
Purpose of the Study:
- To prospectively evaluate the incidence of CMV reactivation after CARTx.
- To identify risk factors associated with CMV reactivation.
- To assess the role of CMV-specific cell-mediated immunity (CMV-CMI) in predicting reactivation.
Main Methods:
- 72 CMV-seropositive adults receiving CARTx were monitored for CMV reactivation weekly up to 12 weeks post-therapy.
- CMV-specific cell-mediated immunity (CMV-CMI) was assessed using an interferon-gamma release assay.
- Cox regression and ROC curves were used to analyze risk factors and predictive performance.
Main Results:
- CMV reactivation occurred in 25% of patients post-CARTx, with no observed end-organ disease.
- BCMA-targeted CARTx and corticosteroid use (>3 days) were significantly associated with increased CMV reactivation risk.
- Lower CMV-CMI at week 2 post-infusion and prior antitumor regimens showed possible associations with reactivation.
Conclusions:
- CMV reactivation is a significant concern after CARTx, particularly with BCMA-targeted therapies and corticosteroid use.
- Targeted CMV surveillance between 2 and 6 weeks post-CARTx is recommended for high-risk patients.
- Further research into CMV-CMI's predictive role may refine monitoring strategies.
Background:
The epidemiology of cytomegalovirus (CMV) after chimeric antigen receptor-modified T-cell immunotherapy (CARTx) is poorly understood owing to a lack of routine surveillance.
Methods:
We prospectively enrolled 72 adult CMV-seropositive CD19-, CD20-, or BCMA-targeted CARTx recipients and tested plasma samples for CMV before and weekly up to 12 weeks after CARTx. We assessed CMV-specific cell-mediated immunity (CMV-CMI) before and 2 and 4 weeks after CARTx, using an interferon γ release assay to quantify T-cell responses to IE-1 and pp65. We tested pre-CARTx samples to calculate a risk score for cytopenias and infection (CAR-HEMATOTOX). We used Cox regression to evaluate CMV risk factors and evaluated the predictive performance of CMV-CMI for CMV reactivation in receiver operator characteristic curves.
Results:
CMV was detected in 1 patient (1.4%) before and in 18 (25%) after CARTx, for a cumulative incidence of 27% (95% confidence interval, 16.8-38.2). The median CMV viral load (interquartile range) was 127 (interquartile range, 61-276) IU/mL, with no end-organ disease observed; 5 patients received preemptive therapy based on clinical results. CMV-CMI values reached a nadir 2 weeks after infusion and recovered to baseline levels by week 4. In adjusted models, BCMA-CARTx (vs CD19/CD20) and corticosteroid use for >3 days were significantly associated with CMV reactivation, and possible associations were detected for lower week 2 CMV-CMI and more prior antitumor regimens. The cumulative incidence of CMV reactivation almost doubled when stratified by BCMA-CARTx target and use of corticosteroids for >3 days (46% and 49%, respectively).
Conclusions:
CMV testing could be considered between 2 and 6 weeks in high-risk CARTx recipients.
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