Cytomegalovirus reactivation after CD19 CAR T-cell therapy is clinically significant

Herr, Megan M.; Nowak, Jan; Ho, Christine M.; Almyroudis, Nikolaos G.; Attwood, Kristopher; Bonnewell, John; Walsh, Marissa; Segal, Brahm H.; Ross, Maureen; McCarthy, Philip L.; Hahn, Theresa

doi:10.3324/haematol.2022.281719

Cited by 19 publications

(17 citation statements)

References 15 publications

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“…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%

“…112 Thus, while the incidence of CMV viremia may be underestimated, the clinical relevance of these events remains unclear with most patients improving, even without preemptive antiviral therapy. Cases of CMV end-organ disease have been described, 36,38,111,[113][114][115][116] but are overall rare considering the widespread use of CAR-T-cell therapy in the United States and globally. However, few studies have evaluated CMV viremia in a systematic fashion in this population and the clinical relevance of asymptomatic reactivation remains unknown.…”

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: Cytomegalovirusmentioning

confidence: 99%

Section: Cytomegalovirusmentioning

confidence: 99%

Section: Cytomegalovirusmentioning

confidence: 99%

Section: Special Considerationsmentioning

confidence: 99%

See 2 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

“…In contrast, CMV in immunocompetent adults is often asymptomatic or may present with fever and mononucleosis-like symptoms. CMV can reactivate from a latent state and replicate in immunocompromised patients, such as those who have received allogeneic transplantation or CAR T cell therapy ( Figure 1 ) ( 5 , 6 ). This reactivation manifests as CMV viremia, and the patient may be febrile, cytopenic, or experience malaise.…”

Section: Is a Persistent Problem After Hctmentioning

confidence: 99%

Another tool against cytomegalovirus after allogeneic hematopoietic cell transplantation

Chen¹,

Shpall²

2023

Journal of Clinical Investigation

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High pretreatment disease burden as a risk factor for infectious complications following CD19 chimeric antigen receptor T‐cell therapy for large B‐cell lymphoma

O'Reilly,

Neill,

Collin

et al. 2024

HemaSphere

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Infection has emerged as the chief cause of non‐relapse mortality (NRM) post CD19‐targeting chimeric antigen receptor T‐cell therapy (CAR‐T) therapy. Even though up to 50% of patients may remain infection‐free, many suffer multiple severe, life‐threatening, or fatal infectious events. The primary aim of this study was to explore severe and life‐threatening infections post licensed CAR‐T therapy in large B‐cell lymphoma, with a focus on the role of disease burden and disease sites in assessing individual risk. We sought to understand the cohort of patients who experience ≥2 infections and those at the highest risk of infectious NRM. Our analysis identifies a higher disease burden after bridging therapy as associated with infection events. Those developing ≥2 infections emerged as a uniquely high‐risk cohort, particularly if the second (or beyond) infection occurred during an episode of immune effector cell‐associated neurotoxicity syndrome (ICANS) or while on steroids and/or anakinra for ICANS. Herein, we also describe the first reported cases of “CAR‐T cold sepsis,” a phenomenon characterized by the lack of an appreciable systemic inflammatory response at the time of detection of infection. We propose a risk‐based strategy to encourage heightened clinician awareness of cold sepsis, with a view to reducing NRM.

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Cytomegalovirus reactivation after CD19 CAR T-cell therapy is clinically significant

Abstract: Not available.

Cited by 19 publications

References 15 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

Another tool against cytomegalovirus after allogeneic hematopoietic cell transplantation

High pretreatment disease burden as a risk factor for infectious complications following CD19 chimeric antigen receptor T‐cell therapy for large B‐cell lymphoma

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