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000293957 1001_ $$0P:(DE-He78)3f4df1d4b15ea8b1daad69322a01e26b$$aFrenking, Jan Hendrik$$b0$$eFirst author$$udkfz
000293957 245__ $$aEASIX-guided risk stratification for complications and outcome after CAR T-cell therapy with ide-cel in relapsed/refractory multiple myeloma.
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000293957 520__ $$aChimeric antigen receptor (CAR) T-cell therapy has demonstrated significant benefits in the treatment of relapsed/refractory multiple myeloma (RRMM). However, these outcomes can be compromised by severe complications, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS) and immune effector cell-associated hematotoxicity (ICAHT), predisposing for life-threatening infections.This retrospective observational study examined a total of 129 patients with RRMM who had received idecabtagene vicleucel (ide-cel) at two major myeloma centers in Germany and one center in the USA to assess the Endothelial Activation and Stress Index (EASIX) as a risk marker for an unfavorable clinical course and outcome after CAR T-cell therapy. EASIX is calculated by lactate dehydrogenase (U/L) × creatinine (mg/dL) / platelets (109 cells/L) and was determined before lymphodepletion (baseline) and at the day of CAR T-cell infusion (day 0). The analysis was extended to EASIX derivatives and the CAR-HEMATOTOX score.An elevated baseline EASIX (>median) was identified as a risk marker for severe late ICAHT, manifesting with an impaired hematopoietic reconstitution and pronounced cytopenias during the late post-CAR-T period. Patients with high EASIX levels (>upper quartile) were particularly at risk, as evidenced by an increased rate of an aplastic phenotype of neutrophil recovery, severe late-onset infections and ICANS. Finally, we found associations between baseline EASIX and an inferior progression-free and overall survival. Moreover, the EASIX at day 0 also demonstrated potential to serve as a risk marker for post-CAR-T complications and adverse outcomes.In conclusion, EASIX aids in risk stratification at clinically relevant time points prior to CAR T-cell therapy with ide-cel. Increased EASIX levels might help clinicians to identify vulnerable patients to adapt peri-CAR-T management at an early stage.
000293957 536__ $$0G:(DE-HGF)POF4-311$$a311 - Zellbiologie und Tumorbiologie (POF4-311)$$cPOF4-311$$fPOF IV$$x0
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000293957 650_7 $$2Other$$achimeric antigen receptor - CAR
000293957 650_7 $$2Other$$acytopenia
000293957 650_7 $$2Other$$aimmunotherapy
000293957 650_7 $$2Other$$amultiple myeloma
000293957 650_7 $$2Other$$atreatment related adverse event - trAE
000293957 650_7 $$08PX1X7UG4D$$2NLM Chemicals$$aidecabtagene vicleucel
000293957 650_7 $$2NLM Chemicals$$aReceptors, Chimeric Antigen
000293957 650_7 $$2NLM Chemicals$$aBiological Products
000293957 650_2 $$2MeSH$$aHumans
000293957 650_2 $$2MeSH$$aMultiple Myeloma: therapy
000293957 650_2 $$2MeSH$$aMultiple Myeloma: immunology
000293957 650_2 $$2MeSH$$aMale
000293957 650_2 $$2MeSH$$aFemale
000293957 650_2 $$2MeSH$$aMiddle Aged
000293957 650_2 $$2MeSH$$aImmunotherapy, Adoptive: adverse effects
000293957 650_2 $$2MeSH$$aImmunotherapy, Adoptive: methods
000293957 650_2 $$2MeSH$$aAged
000293957 650_2 $$2MeSH$$aRetrospective Studies
000293957 650_2 $$2MeSH$$aAdult
000293957 650_2 $$2MeSH$$aReceptors, Chimeric Antigen
000293957 650_2 $$2MeSH$$aRisk Assessment
000293957 650_2 $$2MeSH$$aBiological Products: therapeutic use
000293957 650_2 $$2MeSH$$aTreatment Outcome
000293957 650_2 $$2MeSH$$aCytokine Release Syndrome: etiology
000293957 7001_ $$aZhou, Xiang$$b1
000293957 7001_ $$aWagner, Vivien$$b2
000293957 7001_ $$0P:(DE-He78)743a4a82daab55306a2c88b9f6bf8c2f$$aHielscher, Thomas$$b3$$udkfz
000293957 7001_ $$aKauer, Joseph$$b4
000293957 7001_ $$aMai, Elias K$$b5
000293957 7001_ $$aFriedrich, Mirco J$$b6
000293957 7001_ $$aMichel, Christian S$$b7
000293957 7001_ $$aHajiyianni, Marina$$b8
000293957 7001_ $$aBreitkreutz, Iris$$b9
000293957 7001_ $$aCostello, Patrick$$b10
000293957 7001_ $$aNadeem, Omar$$b11
000293957 7001_ $$0P:(DE-He78)66b39a79f3f922997656d7b902d324fb$$aWeinhold, Niels$$b12$$udkfz
000293957 7001_ $$aGoldschmidt, Hartmut$$b13
000293957 7001_ $$aSchmitt, Anita$$b14
000293957 7001_ $$aLuft, Thomas$$b15
000293957 7001_ $$aSchmitt, Michael$$b16
000293957 7001_ $$aMüller-Tidow, Carsten$$b17
000293957 7001_ $$aTopp, Max$$b18
000293957 7001_ $$aEinsele, Hermann$$b19
000293957 7001_ $$aDreger, Peter$$b20
000293957 7001_ $$aMunshi, Nikhil C$$b21
000293957 7001_ $$aSperling, Adam S$$b22
000293957 7001_ $$aRasche, Leo$$b23
000293957 7001_ $$aSauer, Sandra$$b24
000293957 7001_ $$0P:(DE-He78)1cb537e833afd985097ccfaddffb2ef3$$aRaab, Marc-Steffen$$b25$$eLast author$$udkfz
000293957 773__ $$0PERI:(DE-600)2719863-7$$a10.1136/jitc-2024-009220$$gVol. 12, no. 10, p. e009220 -$$n10$$pe009220$$tJournal for ImmunoTherapy of Cancer$$v12$$x2051-1426$$y2024
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