% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Frenking:293957,
author = {J. H. Frenking$^*$ and X. Zhou and V. Wagner and T.
Hielscher$^*$ and J. Kauer and E. K. Mai and M. J. Friedrich
and C. S. Michel and M. Hajiyianni and I. Breitkreutz and P.
Costello and O. Nadeem and N. Weinhold$^*$ and H.
Goldschmidt and A. Schmitt and T. Luft and M. Schmitt and C.
Müller-Tidow and M. Topp and H. Einsele and P. Dreger and
N. C. Munshi and A. S. Sperling and L. Rasche and S. Sauer
and M.-S. Raab$^*$},
title = {{EASIX}-guided risk stratification for complications and
outcome after {CAR} {T}-cell therapy with ide-cel in
relapsed/refractory multiple myeloma.},
journal = {Journal for ImmunoTherapy of Cancer},
volume = {12},
number = {10},
issn = {2051-1426},
address = {London},
publisher = {BioMed Central},
reportid = {DKFZ-2024-02022},
pages = {e009220},
year = {2024},
note = {#EA:A360#LA:A360#},
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.},
keywords = {Humans / Multiple Myeloma: therapy / Multiple Myeloma:
immunology / Male / Female / Middle Aged / Immunotherapy,
Adoptive: adverse effects / Immunotherapy, Adoptive: methods
/ Aged / Retrospective Studies / Adult / Receptors, Chimeric
Antigen / Risk Assessment / Biological Products: therapeutic
use / Treatment Outcome / Cytokine Release Syndrome:
etiology / chimeric antigen receptor - CAR (Other) /
cytopenia (Other) / immunotherapy (Other) / multiple myeloma
(Other) / treatment related adverse event - trAE (Other) /
idecabtagene vicleucel (NLM Chemicals) / Receptors, Chimeric
Antigen (NLM Chemicals) / Biological Products (NLM
Chemicals)},
cin = {A360 / C060},
ddc = {610},
cid = {I:(DE-He78)A360-20160331 / I:(DE-He78)C060-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39379098},
doi = {10.1136/jitc-2024-009220},
url = {https://inrepo02.dkfz.de/record/293957},
}