1. Academic Validation
  2. Ruxolitinib mitigates steroid-refractory CRS during CAR T therapy

Ruxolitinib mitigates steroid-refractory CRS during CAR T therapy

  • J Cell Mol Med. 2021 Jan;25(2):1089-1099. doi: 10.1111/jcmm.16176.
Jing Pan 1 2 Biping Deng 3 Zhuojun Ling 4 Weiliang Song 4 Jinlong Xu 4 Jiajia Duan 4 Zelin Wang 4 Alex H Chang 5 Xiaoming Feng 1 6 Yue Tan 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
  • 2 State Key Laboratory of Experimental Hematology, Department of Hematology, Beijing Boren Hospital, Beijing, China.
  • 3 Cytology Laboratory, Beijing Boren Hospital, Beijing, China.
  • 4 Department of Hematology, Beijing Boren Hospital, Beijing, China.
  • 5 Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
  • 6 Central Laboratory, Fujian Medical University Union Hospital, Fuzhou, China.
Abstract

Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity are two major CAR T related toxicities. With the interventions of Tocilizumab and Steroids, many patients can recover from severe CRS. However, some patients are refractory to Steroids and develop life-threatening consequences. Ruxolitinib is an oral JAKs inhibitor and promising drug in inflammatory diseases. In this pilot study, we evaluate the efficacy of Ruxolitinib in CRS. Of 14 r/r B-ALL children who received CD19 or CD22 CAR T cell therapies, 4 patients developed severe (≥grade 3) CRS with symptoms that were not alleviated with high-dose Steroids and thus received ruxolitinib. Rapid resolution of CRS symptoms was observed in 4 patients after ruxolitinib treatment. Serum cytokines significantly decreased after ruxolitinib intervention. All patients achieved complete remission on day 30 after infusion, and we could still detect CAR T expansion in vivo despite usage of ruxolitinib. There were no obvious adverse events related to ruxolitinib. In vitro assays revealed that ruxolitinib could dampen CAR T expansion and cytotoxicity, suggesting that the timing and dosage of ruxolitinib should be carefully considered to avoid dampening anti-leukaemia response. Our results suggest that ruxolitinib is active and well tolerated in steroid-refractory and even life-threatening CRS.

Keywords

CAR T cell therapy; acute lymphoblastic leukemia; hematology; immunology; ruxolitinib.

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