Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type
PMID (32600123)
Authors Hu J, Zhang B, Yao F, Fu Y, Chen D, Li D, Du N, Lizaso A, Song J, Zhang L, Li X
Title Acquired multiple mutations ALK I1171N, L1196M and G1202R mediate lorlatinib resistance in EML4-ALK-rearranged malignant pleural mesothelioma: a case report.
Journal Therapeutic advances in respiratory disease
Vol 14
Issue
Date 2020 Jan-Dec
URL
Abstract Text EML4-ALK rearranged malignant pleural mesothelioma (MPM) is rare and its responses to anaplastic lymphoma kinase (ALK) inhibitors, including alectinib and lorlatinib, remain unexplored. In this case report, we describe a patient with EML4-ALK-rearranged stage IIIB MPM who was administered with alectinib and lorlatinib as first-line and fourth-line therapy, respectively. He had remarkable response evaluated as partial response on both regimens lasting approximately 3.5 months on each regimen. His plasma samples were collected during the treatment course and submitted for targeted sequencing to understand the molecular mechanisms of his therapeutic resistance. Sequencing analysis revealed the emergence of ALK I1171N and L1196M at alectinib progression. Meanwhile, ALK I1171N, L1196M, and G1202R mutations were identified at lorlatinib progression, wherein L1196M is confirmed to be in cis to G1202R. We speculate that these multiple mutations synergistically mediated his resistance to both alectinib and lorlatinib. Our report describes the detection of EML4-ALK rearrangement in a patient with MPM who had remarkable therapeutic response with ALK inhibitors. Moreover, our case also revealed acquired mechanisms of lorlatinib resistance mediated by multiple mutations ALK I1171N, L1196M, and G1202R, contributing an incremental step to our understanding of the complexity of acquired resistance mechanisms in sequential ALK inhibitor therapy. The reviews of this paper are available via the supplemental material section.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4 - ALK ALK I1171N ALK L1196M ALK G1202R malignant pleural mesothelioma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK G1202R was identified in the post-progression biopsy of a patient with malignant pleural mesothelioma harboring EML4-ALK with ALK L1196M and ALK I1171N who previously responded to Lorbrena (lorlatinib) treatment (PMID: 32600123). 32600123
EML4 - ALK ALK I1171N ALK L1196M malignant pleural mesothelioma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK L1196M and ALK I1171N were identified in the post-progression biopsy of a patient with malignant pleural mesothelioma harboring EML4-ALK who previously responded to Alecensa (alectinib) treatment (PMID: 32600123). 32600123
EML4 - ALK malignant pleural mesothelioma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in symptom improvement and a partial response lasting 3.5 months in a patient with malignant pleural mesothelioma harboring EML4-ALK (PMID: 32600123). 32600123
EML4 - ALK ALK I1171N ALK L1196M malignant pleural mesothelioma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in tumor regression and a partial response lasting 3.6 months in a patient with malignant pleural mesothelioma harboring EML4-ALK, ALK L1196M, and ALK I1171N (PMID: 32600123). 32600123