Cancer Research and Treatment

Original Article

Lung and Thoracic cancer

Association of Immune-Related Adverse Events and the Efficacy of Anti–PD-(L)1 Monotherapy in Non–Small Cell Lung Cancer: Adjusting for Immortal-Time Bias: Ying Yu, Ning Chen, Sizhe Yu, Wanji Shen, Wanchen Zhai, Hui Li, Yun Fan; Cancer Res Treat. 2024;56(3):751-764. Published online January 2, 2024; DOI: https://doi.org/10.4143/crt.2023.1118

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Purpose
The association between immune-related adverse events (irAEs) and survival outcomes in non–small cell lung cancer (NSCLC) patients treated with programmed death-(ligand) 1 [PD-(L)1] inhibitors remains controversial, partly due to variations in dealing with immortal-time bias (ITB).
Materials and Methods
We retrospectively enrolled 425 advanced NSCLC patients who received anti–PD-(L)1 monotherapy between January 2016 and June 2021, stratifying them into irAE (n=127) and non-irAE (n=298) groups. The primary endpoint was to assess the impact of irAEs on progression-free survival (PFS) and overall survival (OS). Landmark (2-, 3-, 6-, and 9-month) and time-dependent Cox analyses were performed to eliminate ITB.
Results
With a median follow-up of 38.8 months, the occurrence of overall irAEs was significantly associated with superior PFS (11.2 vs. 3.4 months, p < 0.001) and OS (31.4 vs. 14.0 months, p < 0.001), which persisted in landmark and time-dependent Cox analyses. For the main organ-specific irAEs, skin, thyroid, and hepatic irAEs, respectively, showed significantly improved survival compared to the non-irAE group, whereas pneumonitis did not. Single-organ irAEs had the best outcomes compared with multi-organ or no irAE, which also held across subgroups of skin, thyroid, and hepatic irAEs. Moreover, severe grade irAEs and immunotherapy discontinuation had a detrimental effect on survival, systemic steroid therapy showed little effect, while immunotherapy resumption had tolerable safety and a trend of improved survival.
Conclusion
After adequately adjusting ITB, the occurrence of overall irAEs predicts for favorable efficacy of anti–PD-(L)1 monotherapy in NSCLC, with better outcomes observed in patients with skin, thyroid, or hepatic irAEs, particularly those with single-organ involvement.

Citations

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Case Report

Identification of a Novel CSNK2A1-PDGFRB Fusion Gene in a Patient with Myeloid Neoplasm with Eosinophilia: Xiaoyu Xu, Qiongyu Lu, Zheng Wang, Ping Cai, Zhao Zeng, Ling Zhang, Man Wang, Liang Ma, Changgeng Ruan, Suning Chen; Cancer Res Treat. 2021;53(3):889-892. Published online December 24, 2020; DOI: https://doi.org/10.4143/crt.2020.1272

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Platelet-derived growth factor receptor beta (PDGFRB) rearrangements play an important role in the pathogenesis of eosinophilia-associated myeloid/lymphoid neoplasms. Up to now, more than 70 PDGFRB fusions have been identified. Here, a novel PDGFRB fusion gene CSNK2A1-PDGFRB has been identified in myeloproliferative neoplasm (MPN) with eosinophilia by RNA-sequencing, which has been verified by reverse transcription polymerase chain reaction and Sanger sequencing. The new PDGFRB fusion partner gene CSNK2A1 encoded one of the two catalytic subunit of casein kinase II (CK2). To our knowledge, this is the first report on the involvement of CSNK2A1 in fusion genes, especially fusion with another kinase PDGFRB in MPN. In addition, the CSNK2A1-PDGFRB fusion retained the entire kinase domain of PDGFRB and response to imatinib at low concentration. The patient with CSNK2A1-PDGFRB was sensitive to imatinib treatment and acquired sustained complete remission.

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