Journal for ImmunoTherapy of Cancer (Oct 2024)

EASIX-guided risk stratification for complications and outcome after CAR T-cell therapy with ide-cel in relapsed/refractory multiple myeloma

  • Xiang Zhou,
  • Patrick Costello,
  • Anita Schmitt,
  • Carsten Müller-Tidow,
  • Peter Dreger,
  • Michael Schmitt,
  • Max Topp,
  • Hartmut Goldschmidt,
  • Hermann Einsele,
  • Nikhil C Munshi,
  • Marc S Raab,
  • Joseph Kauer,
  • Thomas Hielscher,
  • Niels Weinhold,
  • Mirco J Friedrich,
  • Sandra Sauer,
  • Leo Rasche,
  • Thomas Luft,
  • Jan H Frenking,
  • Vivien Wagner,
  • Elias K Mai,
  • Christian S Michel,
  • Marina Hajiyianni,
  • Iris Breitkreutz,
  • Omar Nadeem,
  • Adam S Sperling

DOI
https://doi.org/10.1136/jitc-2024-009220
Journal volume & issue
Vol. 12, no. 10

Abstract

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Background 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.Methods 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.Results 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.Conclusions 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.