Journal Article

DKFZ-2024-02022

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png EASIX-guided risk stratification for complications and outcome after CAR T-cell therapy with ide-cel in relapsed/refractory multiple myeloma.

Frenking, J. H. (First author)DKFZ* ; Zhou, X. ; Wagner, V. ; Hielscher, T.DKFZ* ; Kauer, J. ; Mai, E. K. ; Friedrich, M. J. ; Michel, C. S. ; Hajiyianni, M. ; Breitkreutz, I. ; Costello, P. ; Nadeem, O. ; Weinhold, N.DKFZ* ; Goldschmidt, H. ; Schmitt, A. ; Luft, T. ; Schmitt, M. ; Müller-Tidow, C. ; Topp, M. ; Einsele, H. ; Dreger, P. ; Munshi, N. C. ; Sperling, A. S. ; Rasche, L. ; Sauer, S. ; Raab, M.-S. (Last author)DKFZ*

2024
BioMed Central London

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Please use a persistent id in citations: doi:10.1136/jitc-2024-009220

Abstract: 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.

Keyword(s): Humans (MeSH) ; Multiple Myeloma: therapy (MeSH) ; Multiple Myeloma: immunology (MeSH) ; Male (MeSH) ; Female (MeSH) ; Middle Aged (MeSH) ; Immunotherapy, Adoptive: adverse effects (MeSH) ; Immunotherapy, Adoptive: methods (MeSH) ; Aged (MeSH) ; Retrospective Studies (MeSH) ; Adult (MeSH) ; Receptors, Chimeric Antigen (MeSH) ; Risk Assessment (MeSH) ; Biological Products: therapeutic use (MeSH) ; Treatment Outcome (MeSH) ; Cytokine Release Syndrome: etiology (MeSH) ; chimeric antigen receptor - CAR ; cytopenia ; immunotherapy ; multiple myeloma ; treatment related adverse event - trAE ; idecabtagene vicleucel ; Receptors, Chimeric Antigen ; Biological Products

Note: #EA:A360#LA:A360#

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Contributing Institute(s):

1. KKE Mol. Hämatologie/Onkologie (A360)
2. C060 Biostatistik (C060)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2024

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Database coverage:
; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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