CAR T-cell treatment during the COVID-19 pandemic: Management strategies and challenges

Hu, Yongxian; Yin, Elaine Tan Su; Yang, Ying‐Ying; Wu, Huitao; Wei, Guoqing; Su, Junwei; Cui, Qu; Jin, Aiyun; Li, Yang; Fu, Shanlin; Zhou, Jianfeng; Qiu, Lugui; Zhang, Xi; Liang, Aibin; Jing, Hongmei; Li, Yuhua; Blaise, Didier; Mohty, Mohamad; Nagler, Arnon; Huang, He

doi:10.1016/j.retram.2020.06.003

Cited by 33 publications

(31 citation statements)

References 24 publications

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“…Wei J. et al reported a MM patient infected with SARS-COV-2 3 month after fully humanized, anti-BCMA CAR-T-cell therapy, he underwent progression of COVID-19 with the elevated levels of cytokine profiles and B-cell aplasia. Unfortunately, after polypharmacy strategy of corticosteroids, cefoperazone/sulbactam, teicoplanin and voriconazole, these patients still maintain a high viral load and died of respiratory failure [40]. Therefore, some recommendations may contribute to reasonable decision-making of CAR-T-cell therapy under the circumstance of COVID-19 pandemic.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, acquired humoral immunity deficiencies (like B-cell aplasia) and myelosuppression after CAR-T-cell infusion possibly increased susceptibility to COVID-19 in those patients, likewise, virus infection is a risk factor associated with cytopenia. These comparable performances and interactions between the two courses pose particular challenges in identification and diagnosing comorbid COVID-19 and hematological malignancies [ 40 ]. Previous reports showed the lack of proved treatments available for treating immunocompromised patients with COVID-19 [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

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Clinical characterization and risk factors associated with cytokine release syndrome induced by COVID-19 and chimeric antigen receptor T-cell therapy

Hong

Zhao

Wang

et al. 2020

Bone Marrow Transplant

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An excessive immune response during coronavirus disease (COVID-19) can induce cytokine release syndrome (CRS), which is associated with life-threatening complications and disease progression. This retrospective study evaluated the clinical characteristics of severe CRS (sCRS, grade 3-4) induced by severe COVID-19 (40 patients) or chimeric antigen receptor T-cell (CAR-T) therapy as a comparator (41 patients). Grade 4 CRS was significantly more common in the COVID-19 group (15/40 (35.7%) vs. 5/41 (12.2%), P = 0.008). The CART group had more dramatic increase in cytokines, including IL-2, IL-6, IL-10, and IFN-γ. Interestingly, COVID-19 group had significantly higher levels for TNF-α (31.1 pg/ ml (16.1-70.0) vs. 3.3 (1.8-9.6), P < 0.001) and lg viral loads were correlated with lg IL-6 (R 2 = 0.101; P < 0.001) and lg IL-10 (R 2 = 0.105; P < 0.001). The independent risk factor for COVID-19-related sCRS was hypertension history (OR: 4.876, 95% CI: 2.038-11.668; P < 0.001). Our study demonstrated that there were similar processes but different intensity of inflammatory responses of sCRS in COVID-19 and CART group. The diagnose and management of severe COVID-19related sCRS can learn lessons from treatment of sCRS induced by CART therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinical characterization and risk factors associated with cytokine release syndrome induced by COVID-19 and chimeric antigen receptor T-cell therapy

Hong

Zhao

Wang

et al. 2020

Bone Marrow Transplant

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“…The use of dasatinib as maintenance therapy post-allogeneic SCT increases the risk of CMV reactivation and pleural effusion ( 28 ). Accordingly, dasatinib should be used with caution during the COVID-19 pandemic ( 9 ).…”

Section: Management Of Patients With Acute Leukemiamentioning

confidence: 99%

“…No significant differences in baseline characteristics were observed between the patients with hematologic malignancies who developed COVID-19 and those who did not. However, COVID-19 appeared to be more severe, and more deaths were reported, in the patients with hematologic malignancies compared to the cohort of healthcare providers who developed Several papers have appeared, by individuals, groups of specialists or under the auspices of scientific societies, to offer an initial description of the clinical presentation of COVID-19 in patients with hematologic malignancies and to advocate for general recommendations of good clinical practice in this pandemic period, for both adult and pediatric patients (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). One interesting case report involved a SARS-CoV-2 infection in a 39-year-old patient with chronic lymphocytic leukemia (CLL) where the clinical and biochemical manifestations of COVID-19 were partly masked by the coexisting CLL (6).…”

Section: Introductionmentioning

confidence: 99%

“…Specific guidelines have been proposed for chimeric antigen receptor T-cell (CART) therapy (9), acute myeloid leukemia and myelodysplastic syndromes (10)(11)(12)(13)(14), infections (15), chronic myeloid leukemia (16), chronic lymphocytic leukemia (17), and use of BTK inhibitors (18), which may have the potential benefit of blunting the hyperinflammatory response to SARS-CoV-2, but also potentially increasing the risk of secondary infections or impaired humoral immunity (18).…”

Section: Introductionmentioning

confidence: 99%

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Management of Patients With Hematologic Malignancies During the COVID-19 Pandemic: Practical Considerations and Lessons to Be Learned

Isidori¹,

Leval

Gergis

et al. 2020

Front. Oncol.

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The COVID-19 pandemic has created unprecedented hurdles to the delivery of care to patients with cancer. Patients with hematologic malignancies appear to have a greater risk of SARS-CoV-2 infection and severe disease due to myelosuppression and lymphopenia. The first challenge, therefore, is how to continue to deliver effective, curative therapy to vulnerable patients and at the same time avoid exposing them, and their health care teams (HCT), to SARS-CoV-2. An additional challenge is the timely completion of the diagnostic and staging studies required to formulate appropriate treatment plans. Deferred procedures and avoidance of multiple trips to the surgical, diagnostic, and laboratory suites require same day consolidation of all procedures. With laboratory medicine absorbed by the need to deploy large scale COVID-testing, the availability of routine molecular tests is affected. Finally, we are increasingly faced with the challenge of making complex treatment decisions in SARS-CoV-2 positive patients with aggressive but potentially curable blood cancers. When to treat, how to treat, when to wait, how long to wait, how to predict and manage toxicities, and how to avoid compromising cure rates remains unknown. We present an outline of the scientific, medical, and operational challenges posed by the COVID-19 pandemic at selected American and European institutions and offer our current view of the key elements of a response. While the peak of the pandemic may be past us, in the absence of a vaccine risks remain, and our alertness and response to future challenges need to be refined and consolidated.

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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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CAR T-cell treatment during the COVID-19 pandemic: Management strategies and challenges

Cited by 33 publications

References 24 publications

Clinical characterization and risk factors associated with cytokine release syndrome induced by COVID-19 and chimeric antigen receptor T-cell therapy

Clinical characterization and risk factors associated with cytokine release syndrome induced by COVID-19 and chimeric antigen receptor T-cell therapy

Management of Patients With Hematologic Malignancies During the COVID-19 Pandemic: Practical Considerations and Lessons to Be Learned

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

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