Incidence, clinical characteristics and prognosis of tumor lysis syndrome following B-cell maturation antigen-targeted chimeric antigen receptor-T cell therapy in relapsed/refractory multiple myeloma

Qiqi Zhang; Cheng Zu; Ruirui Jing; Youqin Feng; Yanlei Zhang; Mingming Zhang; Yuqi Lv; Jiazhen Cui; Linhui Zhou; Ye Meng; Linqin Wang; Zenan Cen; Alex H Chang; Yongxian Hu; He Huang

doi:10.3389/fimmu.2023.1125357

Incidence, clinical characteristics and prognosis of tumor lysis syndrome following B-cell maturation antigen-targeted chimeric antigen receptor-T cell therapy in relapsed/refractory multiple myeloma

Front Immunol. 2023 May 4:14:1125357. doi: 10.3389/fimmu.2023.1125357. eCollection 2023.

Authors

Qiqi Zhang^{1

2

3

4}, Cheng Zu^{1

2

3

4}, Ruirui Jing^{1

2

3

4}, Youqin Feng^{1

2

3

4}, Yanlei Zhang⁵, Mingming Zhang^{1

2

3

4}, Yuqi Lv^{1

2

3

4}, Jiazhen Cui^{1

2

3

4}, Linhui Zhou^{1

2

3

4}, Ye Meng^{1

2

3

4}, Linqin Wang^{1

2

3

4}, Zenan Cen^{1

2

3

4}, Alex H Chang^{5

6}, Yongxian Hu^{1

2

3

4}, He Huang^{1

2

3

4}

Affiliations

¹ Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China.
³ Institute of Hematology, Zhejiang University, Hangzhou, China.
⁴ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China.
⁵ Shanghai YaKe Biotechnology Ltd, Shanghai, China.
⁶ Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Abstract

Background aims: B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T cell (CAR-T) therapy is used for refractory or relapsed multiple myeloma (r/r MM). However, CAR-T-related tumor lysis syndrome (TLS) has been observed. We aimed to elucidate the incidence, clinical and laboratory characteristics, and prognosis of CAR-T cell-related TLS.

Methods: Patients (n=105) with r/r MM treated with BCMA-targeted CAR-T cell therapy were included. Patient characteristics, laboratory parameters, and clinical outcomes were assessed.

Results: Eighteen (17.1%) patients developed TLS after BCMA-targeted CAR-T cell therapy. The median time till TLS onset was 8 days. Patients with TLS had steep rise in uric acid (UA), creatinine, and lactate dehydrogenase (LDH) within 6 days following CAR-T cell infusion and presented earlier and persistent escalation of cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-γ [IFN-γ], and ferritin levels). All 18 patients had cytokine release syndrome (CRS), of which 13 (72.2%) developed grade 3-4 CRS. Three of 18 patients (16.7%) developed immune effector cell-associated neurotoxicity syndrome (ICANS): two patients with grade 1 ICANS and one with grade 2 ICANS. TLS development had a negative effect on the objective response rate (77.8% in the TLS group vs. 95.4% in the non-TLS group, p<0.01). During the median follow-up of 15.1 months, the median PFS was poorer of patients with TLS (median: 3.4 months in the TLS group vs. 14.7 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.5 [95% confidence interval [CI] 1.5-8.5]). Also, TLS development exhibited significant effects on OS (median: 5.0 months in the TLS group vs. 39.8 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.7 [95% CI 1.3-10.3]). TLS was associated with a higher tumor burden, elevated baseline creatinine and UA levels, severe CRS, pronounced CAR-T cell expansion, and corticosteroid use.

Conclusion: TLS is a frequently observed CAR-T therapy complication and negatively influences clinical response and prognosis. Close monitoring for TLS should be implemented during CAR-T cell therapy, especially for those at high TLS risk.

Keywords: B-cell maturation antigen; chimeric antigen receptor-T; immunotherapy; multiple myeloma; tumor lysis syndrome.

Publication types

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

MeSH terms

B-Cell Maturation Antigen
Cell- and Tissue-Based Therapy
Creatinine
Humans
Incidence
Multiple Myeloma* / drug therapy
Prognosis
Receptors, Chimeric Antigen*
Tumor Lysis Syndrome* / etiology
Tumor Lysis Syndrome* / therapy

Substances

Receptors, Chimeric Antigen
cell-associated neurotoxicity
B-Cell Maturation Antigen
Creatinine

Grants and funding

This work was supported by Zhejiang Provincial Key Medical Discipline (Medical Tissue Engineering). We sincerely thank the support from the National Natural Science Foundation of China (81730008).