Cytomegalovirus DNAemia in haematological patients undergoing CD19-directed chimeric antigen receptor T-cell therapy: should it be systematically monitored?

Asunción, Carlos Solano de la; Hernani, Rafael; Albert, Eliseo; Gómez, María Dolores; Giménez, Estela; Benzaquén, Ana; Gonzalez‐Barberá, Eva María; Hernández‐Boluda, Juan Carlos; Pérez, Ariadna; Piñana, José Luís; Chorão, Pedro; Guerreiro, Manuel; Montoro, Juan; Sanz, Jaime; Solano, Carlos; Navarro, David

doi:10.1016/j.cmi.2023.05.010

Cited by 4 publications

(6 citation statements)

References 5 publications

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“…among 95 CMV‐seropositive patients, 42 patients (44%) developed at least one positive CMV PCR test after infusion and 22% had a CMV viral load ≥1000 IU/mL (whole blood samples) 109 . There was no evidence of CMV disease in any patient, 109 which is in agreement with most other studies 57,110 . On multivariable analysis, prior use of dexamethasone was associated with an increased risk for CMV viremia ≥1000 IU/mL 109 …”

Section: Special Considerationssupporting

confidence: 84%

“…The epidemiology of CMV after CAR-T-cell therapy is not well elucidated due to the absence of routine clinical monitoring and the small size and retrospective design of existing studies. 57,[109][110][111] In CD19 CAR-T-cell therapy recipients with lymphoma, CMV viremia has been reported in 17%-44% with variable frequency of testing, duration of follow-up and inclusion criteria (CMV seropositive vs. seronegative). 57,[109][110][111] In the largest study to date by Márquez-Algaba et al among 95 CMV-seropositive patients, 42 patients (44%) developed at least one positive CMV PCR test after infusion and 22% had a CMV viral load ≥1000 IU/mL (whole blood samples).…”

Section: Cytomegalovirusmentioning

confidence: 99%

“…57,[109][110][111] In CD19 CAR-T-cell therapy recipients with lymphoma, CMV viremia has been reported in 17%-44% with variable frequency of testing, duration of follow-up and inclusion criteria (CMV seropositive vs. seronegative). 57,[109][110][111] In the largest study to date by Márquez-Algaba et al among 95 CMV-seropositive patients, 42 patients (44%) developed at least one positive CMV PCR test after infusion and 22% had a CMV viral load ≥1000 IU/mL (whole blood samples). 109 There was no evidence of CMV disease in any patient, 109 which is in agreement with most other studies.…”

Section: Cytomegalovirusmentioning

confidence: 99%

“…109 There was no evidence of CMV disease in any patient, 109 which is in agreement with most other studies. 57,110 On multivariable analysis, prior use of dexamethasone was associated with an increased risk for CMV viremia ≥1000 IU/mL. 109 Even less is known about the epidemiology of CMV after BCMA CAR-T-cell therapy.…”

Section: Cytomegalovirusmentioning

confidence: 99%

“…The epidemiology of CMV after CAR‐T‐cell therapy is not well elucidated due to the absence of routine clinical monitoring and the small size and retrospective design of existing studies 57,109–111 . In CD19 CAR‐T‐cell therapy recipients with lymphoma, CMV viremia has been reported in 17%–44% with variable frequency of testing, duration of follow‐up and inclusion criteria (CMV seropositive vs. seronegative) 57,109–111 .…”

Section: Special Considerationsmentioning

confidence: 99%

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Infections after chimeric antigen receptor (CAR)‐T‐cell therapy for hematologic malignancies

Kampouri,

Little,

Rejeski

et al. 2023

Transplant Infectious Dis

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BackgroundChimeric antigen receptor (CAR)‐T‐cell therapies have revolutionized the management of acute lymphoblastic leukemia, non‐Hodgkin lymphoma, and multiple myeloma but come at the price of unique toxicities, including cytokine release syndrome, immune effector cell‐associated neurotoxicity syndrome, and long‐term “on‐target off‐tumor” effects.MethodsAll of these factors increase infection risk in an already highly immunocompromised patient population. Indeed, infectious complications represent the key determinant of non‐relapse mortality after CAR‐T cells. The temporal distribution of these risk factors shapes different infection patterns early versus late post‐CAR‐T‐cell infusion. Furthermore, due to the expression of their targets on B lineage cells at different stages of differentiation, CD19, and B‐cell maturation antigen (BCMA) CAR‐T cells induce distinct immune deficits that could require different prevention strategies. Infection incidence is the highest during the first month post‐infusion and subsequently decreases thereafter. However, infections remain relatively common even a year after infusion.ResultsBacterial infections predominate early after CD19, while a more equal distribution between bacterial and viral causes is seen after BCMA CAR‐T‐cell therapy, and fungal infections are universally rare. Cytomegalovirus (CMV) and other herpesviruses are increasingly breported, but whether routine monitoring is warranted for all, or a subgroup of patients, remains to be determined. Clinical practices vary substantially between centers, and many areas of uncertainty remain, including CMV monitoring, antibacterial and antifungal prophylaxis and duration, use of immunoglobulin replacement therapy, and timing of vaccination.ConclusionRisk stratification tools are available and may help distinguish between infectious and non‐infectious causes of fever post‐infusion and predict severe infections. These tools need prospective validation, and their integration in clinical practice needs to be systematically studied. image

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Section: Special Considerationssupporting

confidence: 84%

Section: Cytomegalovirusmentioning

confidence: 99%

Section: Cytomegalovirusmentioning

confidence: 99%

Section: Cytomegalovirusmentioning

confidence: 99%

Section: Special Considerationsmentioning

confidence: 99%

See 3 more Smart Citations

Infections after chimeric antigen receptor (CAR)‐T‐cell therapy for hematologic malignancies

Kampouri,

Little,

Rejeski

et al. 2023

Transplant Infectious Dis

View full text Add to dashboard Cite

show abstract

Cytomegalovirus (CMV) Reactivation and CMV-Specific Cell-Mediated Immunity After Chimeric Antigen Receptor T-Cell Therapy

Kampouri,

Ibrahimi,

Xie

et al. 2023

Clinical Infectious Diseases

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Background The epidemiology of cytomegalovirus (CMV) after chimeric antigen receptor-modified T-cell immunotherapy (CARTx) is poorly understood due to lack of routine surveillance. Methods We prospectively enrolled 72 adult CMV-seropositive CD19-, CD20-, or BCMA-targeted CARTx-recipients and tested plasma for CMV pre- and weekly up to twelve weeks post-CARTx. We assessed CMV-cell mediated immunity (CMI) pre-, and at week two and four post-CARTx using an interferon-γ release assay quantifying 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 one patient (1.4%) pre- and 18 patients (25%) post-CARTx for a cumulative incidence of 27% (95% CI, 16.8–38.2). Median CMV viral load was 127 IU/mL (interquartile range (IQR), 61–276), with no end-organ disease observed; five patients received preemptive therapy based on clinical results. CMV-CMI values reached a nadir two weeks post-infusion and recovered to baseline levels by week four. In adjusted models, BCMA-CARTx (versus 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 2–6 weeks in high-risk CARTx-recipients.

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Understanding the Clinical Significance of Cytomegalovirus Viremia After Chimeric Antigen Receptor T-Cell Therapy: Should We be Treating a Value?

Kampouri,

Boeckh,

Hill

2024

Clinical Infectious Diseases

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Cytomegalovirus DNAemia in haematological patients undergoing CD19-directed chimeric antigen receptor T-cell therapy: should it be systematically monitored?

Cited by 4 publications

References 5 publications

Infections after chimeric antigen receptor (CAR)‐T‐cell therapy for hematologic malignancies

Infections after chimeric antigen receptor (CAR)‐T‐cell therapy for hematologic malignancies

Cytomegalovirus (CMV) Reactivation and CMV-Specific Cell-Mediated Immunity After Chimeric Antigen Receptor T-Cell Therapy

Understanding the Clinical Significance of Cytomegalovirus Viremia After Chimeric Antigen Receptor T-Cell Therapy: Should We be Treating a Value?

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