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

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.