A rare KIF5B-ALK fusion variant in a lung adenocarcinoma patient who responded to crizotinib and acquired the ALK L1196M mutation after resistance: a case report

Zeng, Hao; Liu, Yujie; Wang, Weiya; Tang, Yuan; Tian, Panwen; Liu, Weimin

doi:10.21037/apm-20-2081

Cited by 4 publications

(5 citation statements)

References 20 publications

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“…The resistance of TKI and its subsequent relapse have not been reported yet, but it is possible in the future. As reported by Zeng et al ( 23 ), an acquired ALK L1196M mutation was detected 11 months after disease progression while on crizotinib treatment in a case of lung adenocarcinoma with KIF5B-ALK fusion. In this case, the treatment was switched to ceritinib, which was effective on the ALK L1196M mutation.…”

Section: Discussionsupporting

confidence: 67%

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Case report: ALK-positive histiocytosis presented as bilateral synchronous breast masses with long-term remission on crizotinib

Zhou,

Hurtado-Castillo,

Pandey

2023

Front. Med.

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ALK-positive histiocytosis (APH) is a rare type of histiocytic neoplasm with characteristic ALK (Anaplastic Lymphoma Kinase) gene translocation and fusion, with only 27 reported cases in the literature. In this study, we report the first case of synchronous bilateral breast involvement of ALK-positive histiocytosis on initial presentation in a 46-year-old Hispanic woman. APH was diagnosed by the confirmation of clonal histiocyte proliferation with ALK overexpression on IHC and the presence of KIF5B-ALK gene fusion from her breast and lung biopsies. The patient in our study is currently under complete and long-term remission with crizotinib treatment (an ALK inhibitor). This report expands on the clinical manifestation of APH, emphasizes the importance of ALK detection in histiocytic diseases, and provides the efficacy and long-term prognosis of the ALK inhibitor therapy for APH.

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Section: Discussionsupporting

confidence: 67%

“…In terms of cytogenetics, ALK overexpression and rearrangement were found in all APH cases. Out of the 19 ALK fusion-positive cases, 16 of them are positive for KIF5B-ALK ( 6 , 10 , 23 ). Other ALK partners include TPM3, TRIM33 , and EML4 ( 1 , 24 , 25 ).…”

Section: Discussionmentioning

confidence: 99%

Case report: ALK-positive histiocytosis presented as bilateral synchronous breast masses with long-term remission on crizotinib

Zhou,

Hurtado-Castillo,

Pandey

2023

Front. Med.

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“…In non-small cell lung cancer, the most common site for ALK fusion is the fusion of echinoderm microtubule-associated protein-like 4 (EML4) with ALK (21), other rare fusion sites include the fusion of ALK with TFG, KLC1, KIF5B, STRN, TNFAIP3, TNIP2, etc. (22)(23)(24). There were also case reports concerning e cacy of ALK inhibitors on rare ALK fusion previously (22,25).…”

Section: Discussionmentioning

confidence: 99%

“…(22)(23)(24). There were also case reports concerning e cacy of ALK inhibitors on rare ALK fusion previously (22,25). The two cases of rare ALK fusion found in this study were PKNOX-ALK fusion and IGR-ALK fusion cases, and both cases had been treated by crizotinib effectively, with PFS 11.5 months and 5 months respectively.…”

Section: Discussionmentioning

confidence: 99%

A Clinical Research of Ceritinib Treating Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer With Brain Metastasis

Cui

Liu

et al. 2021

Preprint

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Objective As a second-generation oral anaplastic lymphoma kinase (ALK) inhibitor, ceritinib was recommended as posterior line therapy in patients with crizotinib resistance or intolerance. While in the real world, the clinical efficacy and safety of ceritinib, 450mg/d, taken with a low-fat meal in crizotinib resistant patients, especially with brain metastases, are still to be further investigated. Methods This retrospective analysis was conducted on patients with ALK- positive advanced non-small cell lung cancer (NSCLC) between May 2017 and December 2020 in our hospital, who were crizotinib resistant or intolerant. The aim was to analyze the clinical efficacy and safety of ceritinib as posterior line therapy in patients, especially in those with brain metastases, and to further explore the efficacy against rare fusion of ALK and the option after ALK inhibitor resistance. RECIST (1.1) criteria were adopted, and for relevant statistical analysis, RStudio was used. Results Of the 13 cases treated with ceritinib, 8 were treated as second-line therapy, 5 as third-line or fourth-line treatment. Of the total, 12 had brain metastases, 3 had received brain radiotherapy previously, and 1 had received surgical treatment for brain metastases previously. There were 8 cases evaluated as partial remission (PR), 2 evaluated as stable disease (SD), and 3 unevaluable for the response. There were 1 case of PKNOX2-ALK fusion and 1 case of IGR-ALK fusion observed as rare ALK fusion, and intracranial lesions were evaluated as PR for both. There were 6 cases received subsequent targeted therapy after progression of ceritinib, including 5 with alectinib and 1 with ensartinib, all of which showed response. In 13 cases, by the terminal time of follow-up, median progression-free survival (PFS) was 7.4 m, disease control rate (DCR) was 76.92%, overall response rate (ORR) was 61.54%, and median overall survival (OS) was 25.4m. In 12 cases with brain metastasis, 9 were suitable for intracranial response evaluation, of which, 1 case achieved CR for intracranial lesions, 7 achieved PR and 1 SD was observed, ORR was 88.89%, and DCR was 100%. The adverse events rate of any grade was 91.67%, the common adverse events were diarrhea (46.15%), AST level increased (41.67%), ALT level increased (33.33%), increased GGT (33.33%), increased ALP (25.00%), nausea (16.67%), increased creatinine (16.67%). Other reported AEs were cough, vomiting, dizziness, arthralgia and fatigue, 1 case (8.33%) each. Conclusion Ceritinib 450mg taken with taken with low-fat meal showed good efficacy and safety in crizotinib resistant patients with central nervous system metastasis, and also, it is effective in some cases with rare fusion of ALK.

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“…However, neither case reported the sensitivity of KIF5B-ALK to ALK-TKIs. Zeng et al introduced a case of lung adenocarcinoma with rare KIF5B-ALK (intron 20 of KIF5B is connected to intron 20 of ALK) and obtained PFS for 11 months after treatment with crizotinib [ 78 ]. In addition, NGS-ctDNA genomic analysis after craniocerebral progression in the patient suggested the known KIF5B-ALK fusion and ALK exon 23 L1196M missense mutation.…”

Section: Rare Alk Fusions and Therapeutic Advancesmentioning

confidence: 99%

Therapeutic Advances of Rare ALK Fusions in Non-Small Cell Lung Cancer

et al. 2022

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Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and is the leading cause of cancer-related death. Despite advances in chemotherapy and immunotherapy, the prognosis for advanced patients remains poor. The discovery of oncogenic driver mutations, such as anaplastic lymphoma kinase (ALK) mutations, means that a subset of patients has opportunities for targeted therapy. With the improvement of genetic testing coverage, more and more ALK fusion subtypes and ALK partners have been discovered, and more than 90 rare ALK fusion subtypes have been found in NSCLC. However, unlike the common fusion, echinoderm microtubule-associated protein-like 4 (EML4)-ALK, some rare ALK fusions such as striatin (STRN)-ALK and huntingtin interacting protein 1 (HIP1)-ALK, etc., the large-scale clinical data related to its efficacy are still immature. The clinical application of ALK-tyrosine kinase inhibitors (ALK-TKIs) mainly depends on the positivity of the ALK gene, regardless of the molecular characteristics of the fusion partner. Recent clinical studies in the ALK-positive NSCLC population have demonstrated differences in progression-free survival (PFS) among patients based on different ALK fusion subtypes. This article will introduce the biological characteristics of ALK fusion kinase and common detection methods of ALK fusion and focus on summarizing the differential responses of several rare ALK fusions to ALK-TKIs, and propose corresponding treatment strategies, so as to better guide the application of ALK-TKIs in rare ALK fusion population.

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A rare KIF5B-ALK fusion variant in a lung adenocarcinoma patient who responded to crizotinib and acquired the ALK L1196M mutation after resistance: a case report

Cited by 4 publications

References 20 publications

Case report: ALK-positive histiocytosis presented as bilateral synchronous breast masses with long-term remission on crizotinib

Case report: ALK-positive histiocytosis presented as bilateral synchronous breast masses with long-term remission on crizotinib

A Clinical Research of Ceritinib Treating Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer With Brain Metastasis

Therapeutic Advances of Rare ALK Fusions in Non-Small Cell Lung Cancer

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