1. Anakinra for Refractory Cytokine Release Syndrome or Immune Effector Cell-Associated Neurotoxicity Syndrome after Chimeric Antigen Receptor T Cell Therapy
- Author
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National Institutes of Health (US), National Cancer Institute (US), 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-Cibrián, 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, National Institutes of Health (US), National Cancer Institute (US), 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-Cibrián, 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., and Gauthier, Jordan
- Abstract
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
- Published
- 2023