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Analysis Offers Longer-Term Safety Profile of CAR T-Cell Therapy for B-ALL


The findings come from a pooled analysis of the ELIANA and ENSIGN trials, both of which led to the approval of tisagenlecleucel for these patients.

Researchers have published longer-term safety data on chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel when used for the treatment of children and young adults with B-cell acute lymphoblastic leukemia (B-ALL).

The safety findings come from a pooled analysis of ELIANA and ENSIGN, the 2 multicenter trials that led to the approval of tisagenlecleucel for these patients. Together, the analysis offers safety findings from over 130 patients.

Findings were published recently in Journal for Immunotherapy of Cancer.

“Overall, results of this large pooled safety analysis from 2 multicenter studies of tisagenlecleucel establish a comprehensive safety profile in children and young adults with B-ALL in the context of clinical trials performed prior to regulatory approvals, including characterization of rare and long-term events,” commented the researchers. “This analysis, the longest follow-up of the largest dataset in this patient population, provides guidance to clinicians who care for these patients.”

Throughout both studies, most (77%) patients experienced grade 3/4 treatment-related adverse events (AEs), the most common being 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 a median of 3 days after infusion and resolved in a median of 8 days. Tocilizumab or another anti–cytokine therapy was given to 41% of patients a median of 5 days from the 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in grading of CRS and management of CAR T therapy–related AEs since the time of these studies, these data represent a historical reference point for future research in this patient population and help guide the management of complications for patients receiving treatment outside of clinical trials,” explained the researchers, who found that patients with high tumor burden were more likely to experience CRS and patients with severe CRS were more likely to report neurologic 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 baseline neurologic examination prior to infusion, especially for patients with a history of preexisting central nervous system disorder or leukemia.

In general, toxicities typically occurred within 8 weeks of infusion, and then the risk decreased. Other AEs of interest included infections (42%), prolonged cytopenias (40%), and tumor lysis syndrome (4%). According to the researchers, these toxicities, with the exception of B cell aplasia, were usually transient.


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 Immunother Cancer. Published online August 9, 2021. doi:10.1136/jitc-2020-002287

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