Analysis of IL-6 serum levels and CAR T cell-specific digital PCR in the context of cytokine release syndrome

•The increase in serum IL-6 levels in parallel to the clinical manifestation of CRS following CAR-T therapy can contribute to the interpretation of clinical symptoms.•Serum concentrations of CAR-T are measurable by CAR-T-specific sequences by digital droplet PCR in the peripheral blood of CAR-T recipients.•Further studies should explore a possible correlation of the kinetics of CAR-T concentration in the peripheral blood of recipients with the risk for CRS/CRES development. IntroductionChimeric antigen receptor T-cell (CAR-T) therapies are increasingly used to treat relapsed B-cell lymphomas and acute lymphoblastic leukemia. Considering the frequency of cytokine release syndrome and CAR-T–related encephalopathy syndrome (CRS/CRES) after CAR-T administration, strategies enabling timely prediction of impending CRS/CRES are a clinical need.MethodsWe evaluated the dynamics of serum interleukin (IL)-6 levels and CAR-T transgene copy numbers by digital droplet polymerase chain reaction in the peripheral blood of 11 consecutive patients with aggressive B-cell malignancies.ResultsFour of 11 patients developed CRS, and 3 patients had CRES (33%), 2 of them had previous CRS. IL-6 levels increased on the day of clinical manifestation of CRS. All CRS patients had increased IL-6 peak levels (median IL-6 peak 606 pg/mL in CRS patients vs. 22 pg/mL in non-CRS patients, 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 to be at higher risk of developing CRS/CRES.ConclusionThus, the dynamics of CAR-T transgene copy numbers merits 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.