The findings were recently published in the Journal for Immunotherapy of Cancer.
Overall, the results of this large pooled safety analysis of 2 multicenter studies of tisagenlecleucel establish a comprehensive safety profile in children and young adults with B-ALL in the context of clinical studies conducted prior to regulatory approvals, including characterization of rare and prolonged events,” the researchers said. “This analysis, the longest follow-up of the largest data set in this patient population, provides guidance to clinicians caring for these patients.”
In both studies, most (77%) patients experienced Grade 3/4 treatment-related adverse events (AEs), the most common of which is cytokine release syndrome (CRS; 42%) – a well-documented AE associated with CAR T- cell therapy — and febrile neutropenia (28%).
CRS of any grade occurred in 79% of patients with all but 3 cases occurring within 2 weeks of their infusion. The AE occurred median 3 days after infusion and resolved in median 8 days. Tocilizumab or other anti-cytokine therapy was given to 41% of patients, median 5 days from onset of CRS.
The researchers noted that CRS itself was associated with AEs, such as fever, febrile neutropenia, and tachycardia. As a result, they wrote, these AEs may actually be underreported if they were reported under CRS rather than reported as separate AEs.
“Given the evolution in the classification of CRS and the management of CAR T-therapy-related adverse events since the time of these studies, these data provide a historical reference point for future research in this patient population and aid in the management of complications for patients outside of treatment. of clinical trials,” explained the researchers, who found that patients with high tumor burden were more likely to have CRS and patients with severe CRS were more likely to report neurological events.
Neurologic events, another well-documented AE associated with CAR T-cell therapy, were also common, the researchers found, with 36% of patients experiencing 55 neurologic episodes within 8 weeks of infusion. Based on their experience with tisagenlecleucel, the researchers recommend a thorough basic neurologic examination prior to infusion, especially for patients with a history of pre-existing central nervous system disease or leukemia.
In general, toxicities generally occurred within 8 weeks of infusion, and thereafter the risk decreased. Other interesting side effects were infections (42%), prolonged cytopenias (40%) and tumor lysis syndrome (4%). With the exception of B-cell aplasia, these toxicities were mostly transient, according to the researchers.
Levine JE, Grupp SA, Pulsipher MA, et al. Pooled safety analysis of tisagenlecleucel in children and young adults with B-cell acute lymphoblastic leukemia. J Immune cancer. Published online August 9, 2021. doi:10.1136/jitc-2020-002287