Impact of Renal Impairment and Lymphodepletion Regimen on Outcomes after CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma

Research output: Contribution to journal › Research article › Contributed › peer-review

Contributors

  • Nora Grieb - , Leipzig University (Author)
  • Thomas Wiemers - , Leipzig University (Author)
  • Patrick Born - , Leipzig University (Author)
  • David Fandrei - , Leipzig University (Author)
  • Luise Fischer - , Leipzig University (Author)
  • Maximilian Ferle - , Leipzig University, Center for Scalable Data Analytics and Artificial Intelligence (ScaDS.AI) Dresden/Leipzig (Author)
  • Stefan Franke - , Leipzig University (Author)
  • Johannes Keller - , Leipzig University (Author)
  • Song Yau Wang - , Leipzig University (Author)
  • Madlen Jentzsch - , Leipzig University (Author)
  • Carmen Herling - , Leipzig University (Author)
  • Klaus H. Metzeler - , Leipzig University (Author)
  • Marco Herling - , Leipzig University (Author)
  • Simone Heyn - , Leipzig University (Author)
  • Thomas Neumuth - , Leipzig University, Center for Scalable Data Analytics and Artificial Intelligence (ScaDS.AI) Dresden/Leipzig (Author)
  • Uwe Platzbecker - , Department of Internal Medicine I, University Hospital Leipzig, University Hospital Carl Gustav Carus Dresden (Author)
  • Vladan Vučinić - , Leipzig University, Fraunhofer Institute for Cell Therapy and Immunology (Author)
  • Georg Nikolaus Franke - , Leipzig University (Author)
  • Maximilian Merz - , Leipzig University, Memorial Sloan-Kettering Cancer Center (Author)

Abstract

Background: Chimeric antigen receptor (CAR) T cell therapy revolutionized treatment for relapsed/refractory multiple myeloma (RRMM). The standard lymphodepletion (LDP) regimen is fludarabine and cyclophosphamide (Flu/Cy), but bendamustine has shown comparable efficacy with lower toxicity and is a potentially safer option for patients with renal impairment. Objectives: This study retrospectively analyzes clinical outcomes and CAR T-cell dynamics in patients with RRMM receiving idecabtagene vicleucel (Ide-Cel) or ciltacabtagene autoleucel (Cilta-cel), with a particular focus on the impact of renal function and LDP regimen. Study Design: We included a total of 87 patients who received CAR T-cell therapy: 54 with none/mild chronic kidney disease (CKD) and 34 with moderate/severe CKD. LDP consisted of standard-dose Flu/Cy in 67 patients, reduced-dose Flu/Cy in 11 patients, and bendamustine in 9 patients. Toxicity outcomes were monitored over more than 2000 patient-days, capturing over 20,000 individual data points. Results: Patients with moderate/severe CKD received standard Flu/Cy conditioning less frequently (45.5% versus 96.3%, P < .001) and bendamustine-based LDP more often (27.3% vs. 0%, P < .001). In the survival analysis, we found that CKD status alone did not significantly impact outcomes (OS: P = .95; PFS: P = .76). Similarly, when stratified by CAR T-cell product, CKD status did not impact PFS in Ide-Cel recipients (P = .46). In contrast, among Cilta-Cel–treated patients, those with none/mild CKD demonstrated significantly improved PFS (P = .026). LDP regimen had no effect on PFS (P = .21). In Firth’s penalized Cox model, neither CKD nor LDP independently predicted PFS; however, a significant interaction between CKD status and CAR T product was observed (HR 8.82, 95% CI 1.33-100.45, P = .023). Subgroup analyses confirmed that Cilta-Cel conferred superior PFS compared with Ide-Cel in patients with none/mild CKD (P < .001), whereas no benefit was seen in those with moderate/severe CKD. The median absolute lymphocyte count (ALC) nadir was observed on day -1 in patients receiving Flu/Cy (0.033 × 10⁹/L) and on day +1 in those receiving bendamustine (0.059 × 10⁹/L). At the time of CAR T-cell infusion, median ALC was significantly higher in the bendamustine group compared to the complete dosage Flu/Cy cohort (P = .03). Overall CAR T-cell expansion kinetics did not differ according to CKD status or LDP regimen. Notably, at day 7, Cilta-Cel patients had significantly higher CD4 CAR T cell percentages (of total CD3 CAR T cells) compared to Ide-Cel in the none/mild CKD group (P < .001), a difference that persisted through days 14 (P < .001) and 30 (P < .001). Analysis of hematologic toxicities showed that bendamustine-based LDP was associated with lower rates of early N-ICAHT (P = .002) and a higher ANC nadir (P < .001), while rates of CRS and ICANS were similar between groups. Conclusions: These findings provide a signal supporting the feasibility and safety of bendamustine-based lymphodepletion and highlight the prognostic relevance of renal function in Cilta-Cel–treated patients. While Cilta-Cel generally confers superior efficacy compared with Ide-Cel, this advantage may be attenuated in patients with moderate/severe CKD, potentially due to competing risks such as frailty, early toxicity, or impaired cellular fitness.

Details

Original languageEnglish
Article number1319-1334
Number of pages16
JournalTransplantation and cellular therapy
Volume32
Issue number10
Early online date16 May 2026
Publication statusPublished - Oct 2026
Peer-reviewedYes

External IDs

PubMed 42144192

Keywords

Keywords

  • CAR T-cell therapy, Chronic kidney disease, lymphodepletion, Relapsed/refractory multiple myeloma