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

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Pabst Müller, Thomas Niklaus; Joncourt, Raphael; Heini, Alexander; Wiedemann, Gertrud; Seipel, Katja; Jalowiec, Katarzyna Aleksandra; Mansouri Taleghani, Behrouz; Fux, Michaela; Novak, Urban; Porret, Naomi; Zeerleder, Sacha Sergio and Bacher, Vera Ulrike

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0301-472X

Publisher:

Elsevier

Language:

English

Submitter:

Pierrette Durand Lüthi

Date Deposited:

22 Jul 2020 15:07

Last Modified:

22 Aug 2020 01:33

Publisher DOI:

10.1016/j.exphem.2020.07.003

PubMed ID:

32673688

Uncontrolled Keywords:

CAR-T cell therapy IL-6 cytokine release syndrome (CRS) ddPCR

BORIS DOI:

10.7892/boris.145307

URI:

https://boris.unibe.ch/id/eprint/145307

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