Frontiers in Immunology (Apr 2023)

A combination of pre-infusion serum ferritin, CRP and IL-6 predicts outcome in relapsed/refractory multiple myeloma patients treated with CAR-T cells

  • Yang Liu,
  • Yang Liu,
  • Yang Liu,
  • Xingxing Jie,
  • Xingxing Jie,
  • Xingxing Jie,
  • Li Nian,
  • Li Nian,
  • Li Nian,
  • Ying Wang,
  • Ying Wang,
  • Ying Wang,
  • Congyue Wang,
  • Congyue Wang,
  • Congyue Wang,
  • Jin Ma,
  • Jin Ma,
  • Jin Ma,
  • Jingjing Jiang,
  • Jingjing Jiang,
  • Jingjing Jiang,
  • Qingyun Wu,
  • Qingyun Wu,
  • Qingyun Wu,
  • Jianlin Qiao,
  • Jianlin Qiao,
  • Jianlin Qiao,
  • Wei Chen,
  • Wei Chen,
  • Wei Chen,
  • Jiang Cao,
  • Jiang Cao,
  • Jiang Cao,
  • Zhiling Yan,
  • Zhiling Yan,
  • Zhiling Yan,
  • Ming Shi,
  • Hai Cheng,
  • Hai Cheng,
  • Hai Cheng,
  • Feng Zhu,
  • Feng Zhu,
  • Feng Zhu,
  • Wei Sang,
  • Wei Sang,
  • Wei Sang,
  • Depeng Li,
  • Depeng Li,
  • Depeng Li,
  • Chong Chen,
  • Chong Chen,
  • Chong Chen,
  • Kailin Xu,
  • Kailin Xu,
  • Kailin Xu,
  • Zhenyu Li,
  • Zhenyu Li,
  • Zhenyu Li

DOI
https://doi.org/10.3389/fimmu.2023.1169071
Journal volume & issue
Vol. 14

Abstract

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BackgroundChimeric antigen receptor - T (CAR-T) cell therapy has shown remarkable efficacy in patients with relapsed/refractory multiple myeloma (R/R MM). However, a subset of patients still experienced progression or relapse, and the predictors of prognosis are little known. We analyzed the inflammatory markers before CAR-T cell infusion, to clarify their correlation with survival and toxicity.MethodsThis study involved 109 R/R MM patients who received CAR-T therapy between June 2017 and July 2021. Inflammatory markers, including ferritin, c-reactive protein (CRP), and interleukin-6 (IL-6) before CAR-T cell infusion were detected and then categorized by quartiles. Adverse events and clinical outcomes were compared between patients with upper quartile of inflammatory markers and patients with lower three quartiles of inflammatory markers. An inflammatory prognostic index (InPI) based on these three inflammatory markers was developed in this study. Patients were divided into 3 groups according to the InPI score, progression-free survival (PFS) and overall survival (OS) were compared among the groups. In addition, we explored the correlation between cytokine release syndrome (CRS) and pre-infusion inflammatory markers.ResultsWe found that the pre-infusion high ferritin (hazard ratio [HR], 3.382; 95% confidence interval [CI], 1.667 to 6.863; P = .0007), high CRP (HR, 2.043; 95% CI, 1.019 to 4.097; P = .044), and high IL-6 (HR, 3.298; 95% CI, 1.598 to 6.808; P = .0013) were significantly associated with inferior OS. The formula of the InPI score was based on the HR value of these 3 variables. Three risk groups were formed: (good, 0 to 0.5 point; intermediate, 1 to 1.5 points; poor, 2 to 2.5 points). Median OS for patients with good, intermediate, and poor InPI was not reached, 24 months, and 4 months, respectively, and median PFS was 19.1 months, 12.3 months, and 2.9 months, respectively. In the cox proportional hazards model, poor InPI remained an independent prognostic factor for PFS and OS. Pre-infusion ferritin was negatively associated with CAR T-cell expansion normalized to baseline tumor burden. Spearman correlation analysis showed that pre-infusion ferritin and IL-6 levels positively correlated with the grade of CRS (P = .0369 and P = .0117, respectively). The incidence of severe CRS was higher in patients with high IL-6 compared with patients with low IL-6 (26% vs. 9%, P = .0405). Pre-infusion ferritin, CRP and IL-6 were positively correlated with each peak values within the first month after infusion.ConclusionsOur results suggest that patients with elevated inflammation markers before CAR-T cell infusion are more likely to have poor prognosis.

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