First Report of Management of Sequential Small Cell Transformation and ALK I1171T Mutation as Resistance Mechanisms in a Patient With ALK-EML4 Fused Non–Small Cell Lung Adenocarcinoma With a Novel Combination of Temozolomide and Lorlatinib: A Case Report
ALK-EML4 fusion-positive lung adenocarcinomas (LUADs) are effectively treated with ALK tyrosine kinase inhibitors, but most patients eventually develop resistance to these drugs owing to ALK-dependent or independent mechanisms. Endothelial to mesenchymal transformation with SCLC development is an AL...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364323000760 |
| _version_ | 1827893168646914048 |
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| author | Umair Majeed, MD Shenduo Li, MD, PhD Karan Seegobin, MBBS Aziza Nassar, MD Rami Manochakian, MD Yujie Zhao, MD, PhD Yanyan Lou, MD, PhD |
| author_facet | Umair Majeed, MD Shenduo Li, MD, PhD Karan Seegobin, MBBS Aziza Nassar, MD Rami Manochakian, MD Yujie Zhao, MD, PhD Yanyan Lou, MD, PhD |
| author_sort | Umair Majeed, MD |
| collection | DOAJ |
| description | ALK-EML4 fusion-positive lung adenocarcinomas (LUADs) are effectively treated with ALK tyrosine kinase inhibitors, but most patients eventually develop resistance to these drugs owing to ALK-dependent or independent mechanisms. Endothelial to mesenchymal transformation with SCLC development is an ALK-independent mechanism of resistance that has not been previously reported with sequential ALK I1171T mutation while the patient is on treatment for the SCLC. Here, we report the first case of sequential SCLC transformation followed by ALK I1171T mutation in a patient with ALK-EML4 fusion-positive LUAD. After progression on multiple lines of therapy, we describe our experience of managing ALK-mutant LUAD and transformed SCLC with a novel combination of lorlatinib and temozolomide. We also briefly summarize cases of endothelial to mesenchymal transformation ALK-mutant LUAD from the literature. |
| first_indexed | 2024-03-12T21:50:00Z |
| format | Article |
| id | doaj.art-3c73aa028f9b41f9bb76d26b039694fb |
| institution | Directory Open Access Journal |
| issn | 2666-3643 |
| language | English |
| last_indexed | 2024-03-12T21:50:00Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj.art-3c73aa028f9b41f9bb76d26b039694fb2023-07-26T04:09:40ZengElsevierJTO Clinical and Research Reports2666-36432023-07-0147100536First Report of Management of Sequential Small Cell Transformation and ALK I1171T Mutation as Resistance Mechanisms in a Patient With ALK-EML4 Fused Non–Small Cell Lung Adenocarcinoma With a Novel Combination of Temozolomide and Lorlatinib: A Case ReportUmair Majeed, MD0Shenduo Li, MD, PhD1Karan Seegobin, MBBS2Aziza Nassar, MD3Rami Manochakian, MD4Yujie Zhao, MD, PhD5Yanyan Lou, MD, PhD6Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FloridaDivision of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FloridaDivision of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FloridaDivision of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FloridaDivision of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FloridaDivision of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FloridaDivision of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida; Corresponding author. Address for correspondence: Yanyan Lou, MD, PhD, Division of Hematology and Medical Oncology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224.ALK-EML4 fusion-positive lung adenocarcinomas (LUADs) are effectively treated with ALK tyrosine kinase inhibitors, but most patients eventually develop resistance to these drugs owing to ALK-dependent or independent mechanisms. Endothelial to mesenchymal transformation with SCLC development is an ALK-independent mechanism of resistance that has not been previously reported with sequential ALK I1171T mutation while the patient is on treatment for the SCLC. Here, we report the first case of sequential SCLC transformation followed by ALK I1171T mutation in a patient with ALK-EML4 fusion-positive LUAD. After progression on multiple lines of therapy, we describe our experience of managing ALK-mutant LUAD and transformed SCLC with a novel combination of lorlatinib and temozolomide. We also briefly summarize cases of endothelial to mesenchymal transformation ALK-mutant LUAD from the literature.http://www.sciencedirect.com/science/article/pii/S2666364323000760Case reportALK-EML4ALK-positive NSCLCSmall cell transformationALK I1171T mutation |
| spellingShingle | Umair Majeed, MD Shenduo Li, MD, PhD Karan Seegobin, MBBS Aziza Nassar, MD Rami Manochakian, MD Yujie Zhao, MD, PhD Yanyan Lou, MD, PhD First Report of Management of Sequential Small Cell Transformation and ALK I1171T Mutation as Resistance Mechanisms in a Patient With ALK-EML4 Fused Non–Small Cell Lung Adenocarcinoma With a Novel Combination of Temozolomide and Lorlatinib: A Case Report JTO Clinical and Research Reports Case report ALK-EML4 ALK-positive NSCLC Small cell transformation ALK I1171T mutation |
| title | First Report of Management of Sequential Small Cell Transformation and ALK I1171T Mutation as Resistance Mechanisms in a Patient With ALK-EML4 Fused Non–Small Cell Lung Adenocarcinoma With a Novel Combination of Temozolomide and Lorlatinib: A Case Report |
| title_full | First Report of Management of Sequential Small Cell Transformation and ALK I1171T Mutation as Resistance Mechanisms in a Patient With ALK-EML4 Fused Non–Small Cell Lung Adenocarcinoma With a Novel Combination of Temozolomide and Lorlatinib: A Case Report |
| title_fullStr | First Report of Management of Sequential Small Cell Transformation and ALK I1171T Mutation as Resistance Mechanisms in a Patient With ALK-EML4 Fused Non–Small Cell Lung Adenocarcinoma With a Novel Combination of Temozolomide and Lorlatinib: A Case Report |
| title_full_unstemmed | First Report of Management of Sequential Small Cell Transformation and ALK I1171T Mutation as Resistance Mechanisms in a Patient With ALK-EML4 Fused Non–Small Cell Lung Adenocarcinoma With a Novel Combination of Temozolomide and Lorlatinib: A Case Report |
| title_short | First Report of Management of Sequential Small Cell Transformation and ALK I1171T Mutation as Resistance Mechanisms in a Patient With ALK-EML4 Fused Non–Small Cell Lung Adenocarcinoma With a Novel Combination of Temozolomide and Lorlatinib: A Case Report |
| title_sort | first report of management of sequential small cell transformation and alk i1171t mutation as resistance mechanisms in a patient with alk eml4 fused non small cell lung adenocarcinoma with a novel combination of temozolomide and lorlatinib a case report |
| topic | Case report ALK-EML4 ALK-positive NSCLC Small cell transformation ALK I1171T mutation |
| url | http://www.sciencedirect.com/science/article/pii/S2666364323000760 |
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