%0 Journal Article
%A Frenking, Jan Hendrik
%A Zhou, Xiang
%A Wagner, Vivien
%A Hielscher, Thomas
%A Kauer, Joseph
%A Mai, Elias K
%A Friedrich, Mirco J
%A Michel, Christian S
%A Hajiyianni, Marina
%A Breitkreutz, Iris
%A Costello, Patrick
%A Nadeem, Omar
%A Weinhold, Niels
%A Goldschmidt, Hartmut
%A Schmitt, Anita
%A Luft, Thomas
%A Schmitt, Michael
%A Müller-Tidow, Carsten
%A Topp, Max
%A Einsele, Hermann
%A Dreger, Peter
%A Munshi, Nikhil C
%A Sperling, Adam S
%A Rasche, Leo
%A Sauer, Sandra
%A Raab, Marc-Steffen
%T EASIX-guided risk stratification for complications and outcome after CAR T-cell therapy with ide-cel in relapsed/refractory multiple myeloma.
%J Journal for ImmunoTherapy of Cancer
%V 12
%N 10
%@ 2051-1426
%C London
%I BioMed Central
%M DKFZ-2024-02022
%P e009220
%D 2024
%Z #EA:A360#LA:A360#
%X 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.
%K Humans
%K Multiple Myeloma: therapy
%K Multiple Myeloma: immunology
%K Male
%K Female
%K Middle Aged
%K Immunotherapy, Adoptive: adverse effects
%K Immunotherapy, Adoptive: methods
%K Aged
%K Retrospective Studies
%K Adult
%K Receptors, Chimeric Antigen
%K Risk Assessment
%K Biological Products: therapeutic use
%K Treatment Outcome
%K Cytokine Release Syndrome: etiology
%K chimeric antigen receptor - CAR (Other)
%K cytopenia (Other)
%K immunotherapy (Other)
%K multiple myeloma (Other)
%K treatment related adverse event - trAE (Other)
%K idecabtagene vicleucel (NLM Chemicals)
%K Receptors, Chimeric Antigen (NLM Chemicals)
%K Biological Products (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39379098
%R 10.1136/jitc-2024-009220
%U https://inrepo02.dkfz.de/record/293957