Human herpesvirus 6 myelitis after chimeric antigen receptor T-cell therapy

Handley, Guy; Khawaja, Fareed; Kondapi, Divya; Lee, Hun J.; Kaufman, Gregory P.; Neelapu, Sattva S.; Fayad, Luis; Tummala, Sudhakar; Chi, Linda; Mulanovich, Victor E.

doi:10.1016/j.ijid.2021.09.061

Cited by 15 publications

(12 citation statements)

References 13 publications

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“…Testing platforms suffer from a lack of standardization in measurement of HHV-6 DNA levels, and discordance among platforms has been noted [ 23 ]. Additional populations, such as patients following chimeric antigen receptor T-cell therapy, may carry increased risks and require further evaluation [ 20 , 23 ]. In unclear scenarios, ciHHV-6 should be evaluated, but is not yet standard of care in most transplant centers.…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

Current Role of Prospective Monitoring and Preemptive and Prophylactic Therapy for Human Herpesvirus 6 After Allogeneic Stem Cell Transplantation

Handley

2022

Open Forum Infectious Diseases

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Human herpesvirus-6 (HHV-6) frequently reactivates after allogeneic stem cell transplantation (SCT). Most patients are asymptomatic and viremia often resolves without therapy; however, transplant related complications may be associated with reactivation. Multiple presentations have been attributed to HHV-6 reactivation after SCT including encephalitis. Several strategies have been trialed to reduce such risks or complications. Challenges exist with prospective monitoring strategies, and established thresholds of high-level reactivation may be limited. Three published guidelines and extensive trials focusing on pre-emptive and prophylactic strategies are reviewed. Future areas of investigation and high-risk populations are described. Existing trials and testing platforms have significant limitations, and to date no clear benefit for a pre-emptive or prophylactic intervention has been demonstrated.

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Section: Discussion and Future Directionsmentioning

confidence: 99%

Current Role of Prospective Monitoring and Preemptive and Prophylactic Therapy for Human Herpesvirus 6 After Allogeneic Stem Cell Transplantation

Handley

2022

Open Forum Infectious Diseases

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“…In two other cases of HHV‐6 encephalitis following CAR‐T therapy, neurological symptoms were evident, but plasma HHV‐6 PCR remained negative while CSF PCR turned positive. Initiation of ganciclovir led to symptom improvement 86,87 …”

Section: Specific Viral Infection In Car‐t Immunotherapymentioning

confidence: 99%

Improving the safety of CAR‐T‐cell therapy: The risk and prevention of viral infection for patients with relapsed or refractory B‐cell lymphoma undergoing CAR‐T‐cell therapy

Qian,

Yang,

Zhang

et al. 2024

American J Hematol

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Chimeric antigen receptor (CAR) T‐cell therapy, an innovative immunotherapeutic against relapsed/refractory B‐cell lymphoma, faces challenges due to frequent viral infections. Despite this, a comprehensive review addressing risk assessment, surveillance, and treatment management is notably absent. This review elucidates immune response compromises during viral infections in CAR‐T recipients, collates susceptibility risk factors, and deliberates on preventive strategies. In the post‐pandemic era, marked by the Omicron variant, new and severe threats to CAR‐T therapy emerge, necessitating exploration of preventive and treatment measures for COVID‐19. Overall, the review provides recommendations for viral infection prophylaxis and management, enhancing CAR‐T product safety and recipient survival.

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“…The frequent use of corticosteroids for acute toxicities further impacts virus-specific cellular mediated immune responses [ 61 , 62 , 63 ]. Several cases of HHV-6B encephalitis and a case of fatal HHV-6B myelitis after CAR-T cell therapy have been reported [ 40 , 61 , 64 , 65 , 66 , 67 , 68 , 69 ]. However, the epidemiology and clinical significance of HHV-6B reactivation after CAR-T cell therapy are unknown.…”

Section: Epidemiology Of Hhv-6b After Car-t Cell Therapymentioning

confidence: 99%

Human Herpes Virus-6 (HHV-6) Reactivation after Hematopoietic Cell Transplant and Chimeric Antigen Receptor (CAR)- T Cell Therapy: A Shifting Landscape

Kampouri,

Handley,

Hill

2024

Viruses

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HHV-6B reactivation affects approximately half of all allogeneic hematopoietic cell transplant (HCT) recipients. HHV-6B is the most frequent infectious cause of encephalitis following HCT and is associated with pleiotropic manifestations in this setting, including graft-versus-host disease, myelosuppression, pneumonitis, and CMV reactivation, although the causal link is not always clear. When the virus inserts its genome in chromosomes of germ cells, the chromosomally integrated form (ciHHV6) is inherited by offspring. The condition of ciHHV6 is characterized by the persistent detection of HHV-6 DNA, often confounding diagnosis of reactivation and disease—this has also been associated with adverse outcomes. Recent changes in clinical practice in the field of cellular therapies, including a wider use of post-HCT cyclophosphamide, the advent of letermovir for CMV prophylaxis, and the rapid expansion of novel cellular therapies require contemporary epidemiological studies to determine the pathogenic role and spectrum of disease of HHV-6B in the current era. Research into the epidemiology and clinical significance of HHV-6B in chimeric antigen receptor T cell (CAR-T cell) therapy recipients is in its infancy. No controlled trials have determined the optimal treatment for HHV-6B. Treatment is reserved for end-organ disease, and the choice of antiviral agent is influenced by expected toxicities. Virus-specific T cells may provide a novel, less toxic therapeutic modality but is more logistically challenging. Preventive strategies are hindered by the high toxicity of current antivirals. Ongoing study is needed to keep up with the evolving epidemiology and impact of HHV-6 in diverse and expanding immunocompromised patient populations.

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Human herpesvirus 6 myelitis after chimeric antigen receptor T-cell therapy

Cited by 15 publications

References 13 publications

Current Role of Prospective Monitoring and Preemptive and Prophylactic Therapy for Human Herpesvirus 6 After Allogeneic Stem Cell Transplantation

Current Role of Prospective Monitoring and Preemptive and Prophylactic Therapy for Human Herpesvirus 6 After Allogeneic Stem Cell Transplantation

Improving the safety of CAR‐T‐cell therapy: The risk and prevention of viral infection for patients with relapsed or refractory B‐cell lymphoma undergoing CAR‐T‐cell therapy

Human Herpes Virus-6 (HHV-6) Reactivation after Hematopoietic Cell Transplant and Chimeric Antigen Receptor (CAR)- T Cell Therapy: A Shifting Landscape

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