دورية أكاديمية
Anakinra for Refractory Cytokine Release Syndrome or Immune Effector Cell-Associated Neurotoxicity Syndrome after Chimeric Antigen Receptor T Cell Therapy
| العنوان: | Anakinra for Refractory Cytokine Release Syndrome or Immune Effector Cell-Associated Neurotoxicity Syndrome after Chimeric Antigen Receptor T Cell Therapy |
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| المؤلفون: | Gazeau, Nicolas, Liang, Emily C., Wu, Qian “Vicky”, Voutsinas, Jenna M., Barba, Pere, Iacoboni, Gloria, Kwon, Mi, Reguera-Ortega, Juan Luis, López-Corral, Lucía, Hernani, Rafael, Ortiz-Maldonado, Valentín, Martínez-Cibrian, Nuria, Pérez-Martínez, Antonio, Maziarz, Richard T., Williamson, Staci, Nemecek, Eneida R., Shadman, Mazyar, Cowan, Andrew J., Green, Damian J., Kimble, Erik, Hirayama, Alexandre V., Maloney, David G., Turtle, Cameron J., Gauthier, Jordan |
| المساهمون: | National Institutes of Health (US), National Cancer Institute (US) |
| بيانات النشر: | Elsevier American Society for Transplantation and Cellular Therapy |
| سنة النشر: | 2023 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | CAR-T cell therapy, Anakinra, Toxicity, ICANS, CRS |
| الوصف: | Chimeric antigen receptor-engineered (CAR)-T cell therapy remains limited by significant toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The optimal management of severe and/or refractory CRS/ICANS remains ill-defined. Anakinra has emerged as a promising agent based on preclinical data, but its safety and efficacy in CAR-T therapy recipients are unknown. The primary objective of this study was to evaluate the safety of anakinra to treat refractory CRS and ICANS after CAR-T therapy. The secondary objective was to evaluate the impact of key treatment-, patient-, and disease-related variables on the time to CRS/ICANS resolution and treatment-related mortality (TRM). We retrospectively analyzed the outcomes of 43 patients with B cell or plasma cell malignancies treated with anakinra for refractory CRS or ICANS at 9 institutions in the United States and Spain between 2019 and 2022. Cause-specific Cox regression was used to account for competing risks. Multivariable cause-specific Cox regression was used to estimate the effect of anakinra dose on outcomes while minimizing treatment allocation bias by including age, CAR-T product, prelymphodepletion (pre-LD) ferritin, and performance status. Indications for anakinra treatment were grade ≥2 ICANS with worsening or lack of symptom improvement despite treatment with high-dose corticosteroids (n = 40) and grade ≥2 CRS with worsening symptoms despite treatment with tocilizumab (n = 3). Anakinra treatment was feasible and safe; discontinuation of therapy because of anakinra-related side effects was reported in only 3 patients (7%). The overall response rate (ORR) to CAR-T therapy was 77%. The cumulative incidence of TRM in the whole cohort was 7% (95% confidence interval [CI], 2% to 17%) at 28 days and 23% (95% CI, 11% to 38%) at 60 days after CAR-T infusion. The cumulative incidence of TRM at day 28 after initiation of anakinra therapy was 0% in the high-dose (>200 mg/day i.v.) recipient group and ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2666-6375 2666-6367 |
| العلاقة: | https://doi.org/10.1016/j.jtct.2023.04.001Test; Sí; Transplantation and Cellular Therapy 29(7): 430-437 (2023); http://hdl.handle.net/10261/349336Test |
| DOI: | 10.1016/j.jtct.2023.04.001 |
| الإتاحة: | https://doi.org/10.1016/j.jtct.2023.04.001Test http://hdl.handle.net/10261/349336Test |
| حقوق: | none |
| رقم الانضمام: | edsbas.1D6C6F95 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 26666375 26666367 |
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| DOI: | 10.1016/j.jtct.2023.04.001 |