PMID- 38380327 OWN - NLM STAT- MEDLINE DCOM- 20240222 LR - 20240415 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 15 DP - 2024 TI - Case report: Clinical complete response in advanced ALK-positive lung squamous cell carcinoma: a case study of successful anti-PD-1 immunotherapy post ALK-TKIs failure. PG - 1360671 LID - 10.3389/fimmu.2024.1360671 [doi] LID - 1360671 AB - In patients with advanced lung adenocarcinoma (LADC) harboring the echinoderm microtubule-associated protein-like 4 (EML4) -anaplastic lymphoma kinase (ALK) rearrangement, targeted therapy typically demonstrates superior efficacy as an initial treatment compared to chemotherapy. Following resistance to ALK-tyrosine kinase inhibitors (TKIs), regimens incorporating platinum-based dual agents or combined with bevacizumab often show effectiveness. However, therapeutic alternatives become constrained after resistance develops to both TKIs and platinum-based therapies. Given that the majority of ALK-positive non-small cell lung carcinomas (NSCLC) are LADC, the benefits of TKIs for patients with ALK-positive lung squamous cell carcinoma (LSCC) and the optimal treatment strategy for these patients remain a subject of debate. In this case study, we report on a patient with advanced LSCC, in whom the EML4-ALK rearrangement was identified via ARMS-PCR (Amplification Refractory Mutation System-Polymerase Chain Reaction). The patient underwent oral treatment with crizotinib and alectinib, showing effectiveness in both first-line and second-line ALK-TKI therapies, albeit with limited progression-free survival (PFS). Subsequent resistance to second-generation TKI was followed by the detection of tumors in the left neck region via computed tomography (CT). Biopsy pathology revealed non-squamous cell carcinoma, and subsequent treatment with platinum-based double-drug therapy proved ineffective. Further analysis through next-generation sequencing (NGS) indicated ALK negativity but a high expression of programmed death-ligand 1 (PD-L1). Immunotherapy was then initiated, resulting in a PFS of over 29 months and clinical complete remission (cCR). This case underscores the potential benefit of ALK-TKIs in patients with ALK-positive LSCC. Resistance to second-generation TKIs may lead to ALK negativity and histological transformation, highlighting the necessity of repeated biopsies post-TKI resistance for informed treatment decision-making. As of November 2023, imaging studies continue to indicate cCR in the patient, with a survival time exceeding 47 months. CI - Copyright (c) 2024 Yang, Zeng, Zha, Li, Wang, Zhao, Li and Zhang. FAU - Yang, Chen AU - Yang C AD - Zhongshan City People's Hospital, Xinxiang Medical University, Xinxiang, China. AD - Department of Radiotherapy, Zhongshan City People's Hospital, Zhongshan, China. FAU - Zeng, Rui AU - Zeng R AD - Department of Radiotherapy, Zhongshan City People's Hospital, Zhongshan, China. FAU - Zha, Yawen AU - Zha Y AD - Department of Radiotherapy, Zhongshan City People's Hospital, Zhongshan, China. FAU - Li, Yani AU - Li Y AD - Department of Radiotherapy, Zhongshan City People's Hospital, Zhongshan, China. FAU - Wang, Ting AU - Wang T AD - Department of Radiotherapy, Zhongshan City People's Hospital, Zhongshan, China. FAU - Zhao, Ruolan AU - Zhao R AD - Department of Imaging, Zhongshan City People's Hospital, Zhongshan, China. FAU - Li, Minying AU - Li M AD - Department of Radiotherapy, Zhongshan City People's Hospital, Zhongshan, China. FAU - Zhang, Jingjing AU - Zhang J AD - Department of Radiotherapy, Zhongshan City People's Hospital, Zhongshan, China. LA - eng PT - Case Reports PT - Comment PT - Research Support, Non-U.S. Gov't DEP - 20240206 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - 0 (Antineoplastic Agents) RN - 0 (Protein Kinase Inhibitors) SB - IM CON - Zhongguo Fei Ai Za Zhi. 2022 Sep 20;25(9):696-700. PMID: 36172736 MH - Humans MH - Anaplastic Lymphoma Kinase/genetics/metabolism MH - *Lung Neoplasms/diagnosis/drug therapy/genetics MH - Protein-Tyrosine Kinases MH - *Carcinoma, Non-Small-Cell Lung/diagnosis/drug therapy/genetics MH - *Antineoplastic Agents/therapeutic use MH - Protein Kinase Inhibitors/therapeutic use/pharmacology MH - *Carcinoma, Squamous Cell/diagnosis/drug therapy/genetics MH - *Adenocarcinoma of Lung/drug therapy MH - Immunotherapy MH - Lung/pathology PMC - PMC10876774 OTO - NOTNLM OT - ALK-TKI OT - ALK-positive OT - clinical complete response OT - immunotherapy OT - lung squamous cell carcinoma COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/02/21 11:15 MHDA- 2024/02/22 06:42 PMCR- 2024/01/01 CRDT- 2024/02/21 04:08 PHST- 2023/12/23 00:00 [received] PHST- 2024/01/16 00:00 [accepted] PHST- 2024/02/22 06:42 [medline] PHST- 2024/02/21 11:15 [pubmed] PHST- 2024/02/21 04:08 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2024.1360671 [doi] PST - epublish SO - Front Immunol. 2024 Feb 6;15:1360671. doi: 10.3389/fimmu.2024.1360671. eCollection 2024.