EASIX-guided risk stratification for complications and outcome after CAR T-cell therapy with ide-cel in relapsed/refractory multiple myeloma
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 ne...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
07 October 2024
|
| In: |
Journal for ImmunoTherapy of Cancer
Year: 2024, Volume: 12, Issue: 10, Pages: 1-16 |
| ISSN: | 2051-1426 |
| DOI: | 10.1136/jitc-2024-009220 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1136/jitc-2024-009220 Verlag, kostenfrei, Volltext: https://jitc.bmj.com/content/12/10/e009220 
|
| Author Notes: | Jan H. Frenking, Xiang Zhou, Vivien Wagner, Thomas Hielscher, Joseph Kauer, Elias K. Mai, Mirco J. Friedrich, Christian S. Michel, Marina Hajiyianni, Iris Breitkreutz, Patrick Costello, Omar Nadeem, Niels Weinhold, Hartmut Goldschmidt, Anita Schmitt, Thomas Luft, Michael Schmitt, Carsten Müller-Tidow, Max Topp, Hermann Einsele, Peter Dreger, Nikhil C. Munshi, Adam S. Sperling, Leo Rasche, Sandra Sauer, Marc S. Raab |
| Summary: | 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. |
|---|---|
| Item Description: | Gesehen am 06.12.2024 |
| Physical Description: | Online Resource |
| ISSN: | 2051-1426 |
| DOI: | 10.1136/jitc-2024-009220 |