Clinical and radiographic improvement in suspected pulmonary lymphangitic carcinomatosis-associated hypoxemic respiratory failure following iruplinalkib-based treatment in ALK-positive lung adenocarcinoma after sequential treatment with ensartinib and lorlatinib: a two-patient case report
4 affiliations
- 1Central Laboratory, Affiliated Hospital of Putian University, Putian, Fujian, China
- 2Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Putian University, Putian, Fujian, China
- 3Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Putian University, Putian, Fujian, China
- 4School of Basic Medical Sciences, Key Laboratory of Translational Tumor Medicine in Fujian Province, Putian University, Putian, Fujian, China
Abstract
Pulmonary lymphangitic carcinomatosis (PLC) is an uncommon but life-threatening manifestation of advanced lung cancer and may rapidly lead to hypoxemic respiratory failure. Evidence guiding subsequent anaplastic lymphoma kinase (ALK)-directed therapy after prior exposure to multiple ALK tyrosine kinase inhibitors remains limited, particularly in patients with acute respiratory compromise. In this report, we describe two never-smoking women with stage IVB ALK-positive lung adenocarcinoma who developed type I respiratory failure. This was accompanied by clinical and radiographic findings suggestive of PLC after sequential treatment with ensartinib and lorlatinib. Case 1 achieved a partial response to first-line treatment with ensartinib for approximately 19 months. At progression, plasma next-generation sequencing identified an EML4–ALK variant 1 fusion with an acquired ALK p.L1196M resistance mutation. During subsequent lorlatinib therapy, the patient developed rapidly progressive dyspnea, diffuse bilateral peribronchovascular and reticular opacities suggestive of PLC according to radiographic findings, and type I respiratory failure. Rapid improvement in oxygenation was observed following initiation of third-line iruplinalkib monotherapy. Case 2 had ALK-positive lung adenocarcinoma with an intravascular tumor thrombus on diagnostic biopsy. After ensartinib discontinuation due to grade 3 constipation and subsequent lorlatinib therapy, the patient developed type I respiratory failure, pleural effusion, and progressive bilateral pulmonary abnormalities suggestive of PLC according to radiographic findings. Iruplinalkib was administered in combination with salvage pemetrexed. Following initiation of the respective treatment regimens, both patients showed rapid improvement in oxygenation and radiographic observations of pulmonary abnormalities. Case 1 received iruplinalkib monotherapy, whereas case 2 received iruplinalkib and pemetrexed; therefore, treatment-specific attribution was not possible in case 2. No adverse events attributable to iruplinalkib were observed. In these two patients, initiation of iruplinalkib-based treatment was followed by rapid improvement in clinical and radiographic findings, supporting further evaluation of this treatment strategy in similar critically ill patients.
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BibTeX
@article{lin2026clinical,
title = {{Clinical and radiographic improvement in suspected pulmonary lymphangitic carcinomatosis-associated hypoxemic respiratory failure following iruplinalkib-based treatment in ALK-positive lung adenocarcinoma after sequential treatment with ensartinib and lorlatinib: a two-patient case report}},
author = {Hanbin Lin and Yuxiong Hu and Haoqiang Li and Zhongshan Yang and Ying Zhang and Ruina Luan and Qingyu Lin and Maohe Chen},
journal = {Frontiers in Medicine},
year = {2026},
month = oct,
doi = {10.3389/fmed.2026.1917214},
url = {https://doi.org/10.3389/fmed.2026.1917214},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Clinical and radiographic improvement in suspected pulmonary lymphangitic carcinomatosis-associated hypoxemic respiratory failure following iruplinalkib-based treatment in ALK-positive lung adenocarcinoma after sequential treatment with ensartinib and lorlatinib: a two-patient case report
AU - Hanbin Lin
AU - Yuxiong Hu
AU - Haoqiang Li
AU - Zhongshan Yang
AU - Ying Zhang
AU - Ruina Luan
AU - Qingyu Lin
AU - Maohe Chen
PY - 2026
DA - 2026/10/13
JO - Frontiers in Medicine
DO - 10.3389/fmed.2026.1917214
UR - https://doi.org/10.3389/fmed.2026.1917214
AB - Pulmonary lymphangitic carcinomatosis (PLC) is an uncommon but life-threatening manifestation of advanced lung cancer and may rapidly lead to hypoxemic respiratory failure. Evidence guiding subsequent anaplastic lymphoma kinase (ALK)-directed therapy after prior exposure to multiple ALK tyrosine kinase inhibitors remains limited, particularly in patients with acute respiratory compromise. In this report, we describe two never-smoking women with stage IVB ALK-positive lung adenocarcinoma who developed type I respiratory failure. This was accompanied by clinical and radiographic findings suggestive of PLC after sequential treatment with ensartinib and lorlatinib. Case 1 achieved a partial response to first-line treatment with ensartinib for approximately 19 months. At progression, plasma next-generation sequencing identified an EML4–ALK variant 1 fusion with an acquired ALK p.L1196M resistance mutation. During subsequent lorlatinib therapy, the patient developed rapidly progressive dyspnea, diffuse bilateral peribronchovascular and reticular opacities suggestive of PLC according to radiographic findings, and type I respiratory failure. Rapid improvement in oxygenation was observed following initiation of third-line iruplinalkib monotherapy. Case 2 had ALK-positive lung adenocarcinoma with an intravascular tumor thrombus on diagnostic biopsy. After ensartinib discontinuation due to grade 3 constipation and subsequent lorlatinib therapy, the patient developed type I respiratory failure, pleural effusion, and progressive bilateral pulmonary abnormalities suggestive of PLC according to radiographic findings. Iruplinalkib was administered in combination with salvage pemetrexed. Following initiation of the respective treatment regimens, both patients showed rapid improvement in oxygenation and radiographic observations of pulmonary abnormalities. Case 1 received iruplinalkib monotherapy, whereas case 2 received iruplinalkib and pemetrexed; therefore, treatment-specific attribution was not possible in case 2. No adverse events attributable to iruplinalkib were observed. In these two patients, initiation of iruplinalkib-based treatment was followed by rapid improvement in clinical and radiographic findings, supporting further evaluation of this treatment strategy in similar critically ill patients.
SN - 2296-858X
ER -