Toxicity
All 108 treated patients in Phase 1 and 2 of ZUMA-1 trial had adverse events, and 106 (98%) had grade ≥ 3 adverse events. The most common (≥ 10%) Grade 3 ≥ or higher reactions included febrile neutropenia, fever, CRS, encephalopathy, infections with pathogen unspecified, hypotension, hypoxia, and lung infections. 52 (48%) of 108 patients had grade ≥ 3 serious adverse events. The most common serious adverse reactions (> 2%) included encephalopathy, fever, lung infection, febrile neutropenia, cardiac arrhythmia, cardiac failure, urinary tract infection, renal insufficiency, aphasia, cardiac arrest, Clostridium difficile infection, delirium, hypotension, and hypoxia.r
Cytokine release syndrome (CRS) and neurological toxicities (now known as immune effector cell associated neurotoxicity syndrome, ICANS) are potentially life-threatening or fatal adverse events that can occur after Axi-cel infusion. CRS occurred in 101 (94%) of patients, including ≥ Grade 3 CRS in 13%. The median time to onset of CRS was 2 days (range: 1 to 12 days), and the median duration was 7 days (range: 2 to 58 days). Neurological toxicities occurred in 87% (94 of 108) of patients with LBCL, including ≥ Grade 3 cases in 31%. The median time to onset was 4 days (range: 1 to 43 days), and the median duration was 17 days. 43% of patients received tocilizumab, and 27% received glucocorticoids for the management of the cytokine release syndrome, neurologic events, or both.r
Severe and prolonged cytopenias can occur following Axi-cel infusion. Grade ≥ 3 cytopenias occurred in 86% of patients (40% thrombocytopenia, 80% neutropenia, 45% anaemia). Grade ≥ 3 cytopenias were present at day 30 or beyond in 38% of patients (24% thrombocytopenia, 26% neutropenia, 11% anaemia), and at month 3 or beyond in 17% of patients (7% thrombocytopenia, 11% neutropenia, 3% anaemia).r
There were 50 deaths due to progressive disease (46% of patients), and four deaths due to adverse events (two related to Axi-cel and two unrelated to Axi-cel). Of the two treatment-related deaths, one was due to haemophagocytic lymphohistiocytosis and other due to cardiac arrest.r