Efficacy and safety of programmed cell death receptor 1 inhibition-based regimens in patients with pediatric malignancies: the real-world study in China

Ye Hong; Mengjia Song; Yingxia Lan; Juan Wang; Suying Lu; Yu Zhang; Jia Zhu; Feifei Sun; Junting Huang; Juan Liu; Jiaqian Xu; Yanpeng Wu; Haixia Guo; Ruiqing Cai; Zijun Zhen; Yi Que; Yizhuo Zhang

doi:10.3389/fimmu.2023.1182751

Efficacy and safety of programmed cell death receptor 1 inhibition-based regimens in patients with pediatric malignancies: the real-world study in China

Front Immunol. 2023 Jun 9:14:1182751. doi: 10.3389/fimmu.2023.1182751. eCollection 2023.

Authors

Ye Hong^{1

2}, Mengjia Song^{1

2}, Yingxia Lan^{1

2}, Juan Wang^{1

2}, Suying Lu^{1

2}, Yu Zhang^{1

2}, Jia Zhu^{1

2}, Feifei Sun^{1

2}, Junting Huang^{1

2}, Juan Liu³, Jiaqian Xu³, Yanpeng Wu³, Haixia Guo⁴, Ruiqing Cai^{1

2}, Zijun Zhen^{1

2}, Yi Que^{1

2}, Yizhuo Zhang^{1

2}

Affiliations

¹ State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
² Department of Pediatric Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
³ Department of Pediatric, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guang Dong, China.
⁴ Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Abstract

Background: Programmed death receptor 1 (PD-1) inhibition has shown durable response and mild adverse events (AEs) in adult malignancies. However, data on the clinical activity of PD-1 inhibition in pediatric patients are lacking. We comprehensively assessed the efficacy and safety of PD-1 inhibitor-based regimens for pediatric malignancies.

Methods: We conducted a real-world, multi-institutional, retrospective analysis of pediatric malignancies treated with PD-1 inhibitor-based regimens. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints included disease control rate (DCR), duration of response (DOR), and AEs. The Kaplan-Meier method was used to calculate PFS and DOR. The National Cancer Institute Common Toxicity Criteria for AEs (version 5.0) were used to grade toxicity.

Results: A total of 93 and 109 patients were evaluated for efficacy and safety, respectively. For all efficacy-evaluable patients, PD-1 inhibitor monotherapy, combined chemotherapy, combined histone deacetylase inhibitor, and combined vascular endothelial growth factor receptor tyrosine kinase inhibitor cohorts, the ORR and DCR were 53.76%/81.72%, 56.67%/83.33%, 54.00%/80.00%, 100.00%/100.00%, and 12.50%/75.00%, respectively; the median PFS and DOR were 17.6/31.2 months, not achieved/not achieved, 14.9/31.2 months, 17.6/14.9 months, and 3.7/1.8 months, respectively; the incidence rate of AEs were 83.49%, 55.26%, 100.00%, 80.00%, and 100.00%, respectively. One patient in the PD-1 inhibitor-combined chemotherapy cohort discontinued treatment due to diabetic ketoacidosis.

Conclusions: This largest retrospective analysis demonstrate that PD-1 inhibitor-based regimens are potentially effective and tolerable in pediatric malignancies. Our findings provide references for future clinical trials and practice of PD-1 inhibitors in pediatric cancer patients.

Keywords: PD-1 inhibitor-based treatment; PD-1 inhibitors; efficacy; pediatric malignancies; safety.

Publication types

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

MeSH terms

Adult
Apoptosis
Carcinoma, Non-Small-Cell Lung* / drug therapy
Child
Humans
Immune Checkpoint Inhibitors / therapeutic use
Lung Neoplasms* / drug therapy
Programmed Cell Death 1 Receptor
Retrospective Studies
Vascular Endothelial Growth Factor A

Substances

Immune Checkpoint Inhibitors
Programmed Cell Death 1 Receptor
Vascular Endothelial Growth Factor A

Grants and funding

This work was supported by the Key Technology Research Project of Guangzhou Science, Technology and Innovation Committee [grant number 201902020001].