Pabst, Thomas; Joncourt, Raphael; Shumilov, Evgenii; Heini, Alexander; Wiedemann, Gertrud; Legros, Myriam; Seipel, Katja; Schild, Christof; Jalowiec, Katarzyna; Mansouri, Behrouz; Fux, Michaela; Novak, Urban; Porret, Naomi; Zeerleder, Sacha; Bacher, Vera (2020). Analysis of IL-6 serum levels and CAR-T cell specific digital PCR in the context of cytokine release syndrome (CRS). Experimental hematology, 88, 7-14.e3. Elsevier 10.1016/j.exphem.2020.07.003
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CAR-T cell therapies are more and more frequently applied for relapsed B-cell lymphomas and acute lymphoblastic leukemia. Considering the frequency of cytokine release and CAR-T-cell related encephalopathy syndrome (CRS/CRES) following CAR-T administration, strategies enabling timely prediction of impending CRS/CRES are a clinical need. We evaluated the dynamics of serum IL-6 levels and CAR-T transgene copy numbers by digital droplet PCR (ddPCR) in the peripheral blood of eleven consecutive patients with aggressive B-cell malignancies. Four of eleven patients developed CRS, and three patients had CRES (33%), with two of them with previous CRS. IL-6 levels raised on the day of clinical manifestation of CRS. All CRS patients showed increased IL-6 peak levels (median IL-6 peak 606 in CRS patients vs. 22 pg/ml in non-CRS; p=0.0061). Different patterns emerged from the dynamics of CAR-T/µg genomic DNA: "rapid increase and rapid decrease with complete disappearance", "rapid increase and slow decrease with higher persistence", "rapid increase and rapid decrease with lower persistence", and "slow increase and rapid decrease with almost disappearance". Patients with the pattern "rapid increase and slow decrease with higher persistence" of CAR-T/µg genomic DNA concentration seemed at higher risk to develop CRS/CRES. Thus, dynamics of CAR-T transgene copy numbers merit further evaluation for a possible association with manifestation of CRS. Increased IL-6 serum levels at CRS manifestation may contribute to the interpretation of symptoms.
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