All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the Lymphoma Coalition.
Introducing
Now you can personalise
your Lymphoma Hub experience!
Bookmark content to read later
Select your specific areas of interest
View content recommended for you
Find out moreThe Lymphoma Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the Lymphoma Hub cannot guarantee the accuracy of translated content. The Lymphoma Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.
The Lymphoma & CLL Hub is an independent medical education platform, sponsored by Beigene and Roche, and supported through educational grants from Bristol Myers Squibb, Ipsen Biopharmaceuticals, Lilly, Pfizer, and Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC View funders.
Bookmark this article
On Sunday 2nd April, during the “CTSY02 - Immuno-oncology Biomarkers in Clinical Trials” session, Frederick L. Locke, MD, of the H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, gave a talk titled “Immune signatures of cytokine release syndrome and neurologic events in a multicenter registrational trial (ZUMA-1) in subjects with refractory diffuse large B-cell lymphoma treated with axicabtagene ciloleucel (KTE-C19).”
Dr. Locke began the talk by explaining what Cytokine Release Syndrome (CRS) and neurologic events are. They are two potentially serious AEs that are associated with treatment with Chimeric Antigen Receptor (CAR) T-cells. CRS is mediated by high levels of IL-6 and other inflammatory cytokines, and symptoms include hypoxia, hypotension, tachycardia, and fever. Neurologic events are linked to high levels of cytokines or CAR T-cells, and symptoms include seizures, aphasia, tremor, encephalopathy, and confusion. The anti-IL-6 receptor antagonist, tocilizumab, and/or corticosteroids to suppress the immune system are used to manage neurologic events and CRS.
Following this, a brief overview of the ZUMA-1 prospective biomarker analysis, based on 101 treated patients, was given:
The manufacturing success rate of axi-cel was 99%, despite heterogeneity in starting apheresis material (14% naïve, 15% effector, 27% central memory, and 38% effector memory).
Dr. Locke went on to state that levels of CAR T-cells were reported to peak within 7–14 days of treatment with Axi-cel. It was also reported that CAR T-cell expansion is associated with objective response (P = 0.0002) as well as ≥grade 3 neurologic events (P = 0.0028).
Distinct biomarkers also peaked within 7 days of treatment with Axi-cel. Analytes were elevated in ≥50% of patients with ≥2-fold induction above baseline out of a panel of 44 measured. Biomarkers found to associate with ≥grade 3 CRS and neurologic events included, but were not limited to, IL-15, IL-10, and granzyme B. However, IL-2, GM-CSF, and ferritin were found to only associate with neurologic events.
Dr. Locke concluded the talk with a concise summary slide:
Understanding your specialty helps us to deliver the most relevant and engaging content.
Please spare a moment to share yours.
Please select or type your specialty
Your opinion matters
Subscribe to get the best content related to lymphoma & CLL delivered to your inbox