TY  - JOUR
AU  - Frenking, Jan Hendrik
AU  - Zhou, Xiang
AU  - Wagner, Vivien
AU  - Hielscher, Thomas
AU  - Kauer, Joseph
AU  - Mai, Elias K
AU  - Friedrich, Mirco J
AU  - Michel, Christian S
AU  - Hajiyianni, Marina
AU  - Breitkreutz, Iris
AU  - Costello, Patrick
AU  - Nadeem, Omar
AU  - Weinhold, Niels
AU  - Goldschmidt, Hartmut
AU  - Schmitt, Anita
AU  - Luft, Thomas
AU  - Schmitt, Michael
AU  - Müller-Tidow, Carsten
AU  - Topp, Max
AU  - Einsele, Hermann
AU  - Dreger, Peter
AU  - Munshi, Nikhil C
AU  - Sperling, Adam S
AU  - Rasche, Leo
AU  - Sauer, Sandra
AU  - Raab, Marc-Steffen
TI  - EASIX-guided risk stratification for complications and outcome after CAR T-cell therapy with ide-cel in relapsed/refractory multiple myeloma.
JO  - Journal for ImmunoTherapy of Cancer
VL  - 12
IS  - 10
SN  - 2051-1426
CY  - London
PB  - BioMed Central
M1  - DKFZ-2024-02022
SP  - e009220
PY  - 2024
N1  - #EA:A360#LA:A360#
AB  - Chimeric antigen receptor (CAR) T-cell therapy has demonstrated significant benefits in the treatment of relapsed/refractory multiple myeloma (RRMM). However, these outcomes can be compromised by severe complications, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS) and immune effector cell-associated hematotoxicity (ICAHT), predisposing for life-threatening infections.This retrospective observational study examined a total of 129 patients with RRMM who had received idecabtagene vicleucel (ide-cel) at two major myeloma centers in Germany and one center in the USA to assess the Endothelial Activation and Stress Index (EASIX) as a risk marker for an unfavorable clinical course and outcome after CAR T-cell therapy. EASIX is calculated by lactate dehydrogenase (U/L) × creatinine (mg/dL) / platelets (109 cells/L) and was determined before lymphodepletion (baseline) and at the day of CAR T-cell infusion (day 0). The analysis was extended to EASIX derivatives and the CAR-HEMATOTOX score.An elevated baseline EASIX (>median) was identified as a risk marker for severe late ICAHT, manifesting with an impaired hematopoietic reconstitution and pronounced cytopenias during the late post-CAR-T period. Patients with high EASIX levels (>upper quartile) were particularly at risk, as evidenced by an increased rate of an aplastic phenotype of neutrophil recovery, severe late-onset infections and ICANS. Finally, we found associations between baseline EASIX and an inferior progression-free and overall survival. Moreover, the EASIX at day 0 also demonstrated potential to serve as a risk marker for post-CAR-T complications and adverse outcomes.In conclusion, EASIX aids in risk stratification at clinically relevant time points prior to CAR T-cell therapy with ide-cel. Increased EASIX levels might help clinicians to identify vulnerable patients to adapt peri-CAR-T management at an early stage.
KW  - Humans
KW  - Multiple Myeloma: therapy
KW  - Multiple Myeloma: immunology
KW  - Male
KW  - Female
KW  - Middle Aged
KW  - Immunotherapy, Adoptive: adverse effects
KW  - Immunotherapy, Adoptive: methods
KW  - Aged
KW  - Retrospective Studies
KW  - Adult
KW  - Receptors, Chimeric Antigen
KW  - Risk Assessment
KW  - Biological Products: therapeutic use
KW  - Treatment Outcome
KW  - Cytokine Release Syndrome: etiology
KW  - chimeric antigen receptor - CAR (Other)
KW  - cytopenia (Other)
KW  - immunotherapy (Other)
KW  - multiple myeloma (Other)
KW  - treatment related adverse event - trAE (Other)
KW  - idecabtagene vicleucel (NLM Chemicals)
KW  - Receptors, Chimeric Antigen (NLM Chemicals)
KW  - Biological Products (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39379098
DO  - DOI:10.1136/jitc-2024-009220
UR  - https://inrepo02.dkfz.de/record/293957
ER  -