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

doi:10.3389/fimmu.2023.1169071

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

Front Immunol. 2023 Apr 19:14:1169071. doi: 10.3389/fimmu.2023.1169071. eCollection 2023.

Authors

Yang Liu^{1

2

3}, Xingxing Jie^{1

2

3}, Li Nian^{1

2

3}, Ying Wang^{1

2

3}, Congyue Wang^{1

2

3}, Jin Ma^{1

2

3}, Jingjing Jiang^{1

2

3}, Qingyun Wu^{1

2

3}, Jianlin Qiao^{1

2

3}, Wei Chen^{1

2

3}, Jiang Cao^{1

2

3}, Zhiling Yan^{1

2

3}, Ming Shi⁴, Hai Cheng^{1

2

3}, Feng Zhu^{1

2

3}, Wei Sang^{1

2

3}, Depeng Li^{1

2

3}, Chong Chen^{1

2

3}, Kailin Xu^{1

2

3}, Zhenyu Li^{1

2

3}

Affiliations

¹ Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
² Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
³ Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, Jiangsu, China.
⁴ Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.

Abstract

Background: Chimeric 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.

Methods: This 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.

Results: We 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.

Conclusions: Our results suggest that patients with elevated inflammation markers before CAR-T cell infusion are more likely to have poor prognosis.

Keywords: chimeric antigen receptor T cell; inflammation; multiple myeloma; prognostic predictor; relapsed/refractory.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

C-Reactive Protein
Humans
Immunotherapy, Adoptive*
Interleukin-6
Multiple Myeloma* / drug therapy
Neoplasm Recurrence, Local
Receptors, Chimeric Antigen / therapeutic use
T-Lymphocytes

Substances

C-Reactive Protein
Interleukin-6
Receptors, Chimeric Antigen

Grants and funding

This work was supported by funding from the National Natural Science Foundation of China (grant 81770223, 82171762 and 82270232), Research and practice innovation program for Postgraduates of Jiangsu Province (KYCX22_2940).