A 56-year-old Chinese male smoker was diagnosed with stage IV NSCLC in December 2019. His chest CT scan (Figure 1A and B) revealed a mass in the right lower lobe and right-side pleural effusion. PET-CT indicated a mass in the right lower hilar region with an elevated standardized uptake value (SUV) (Figure 1C), multiple lymph node enlargement, and bone metastases (Figure 1D). A diagnosis of lung adenocarcinoma was made on endobronchial ultrasound-guided transbronchial needle aspiration (TBNA-EBUS) of lymph nodes (Figure 1E). Lung adenocarcinoma cells were also found in pleural effusion samples (Figure 1F). Next generation sequencing (NGS) of peripheral blood ctDNA indicated EML4-ALK, variant 2 (E20-A20). Alectinib was given orally, at a dose of 600 mg twice daily from January 7, 2020, which resulted in partial response and patient continued to respond after four months of treatment (Figure 2A and B). He was noted to have an increased total bilirubin (TBIL) of 59.2 mumol/L on May 5, 2020 (on alectinib for 119 days) but did not refer to the doctor.
On May 29, 2020, the patient presented with jaundice, pruritus and fatigue. His Karnofsky performance status (KPS) rating fell to 60 points. The laboratory result showed TBIL 315.0 mumol/L, DBIL (direct bilirubin) 260.7 mumol/L, and IBIL (indirect bilirubin) 54.3 mumol/L. Serum ALP (alkaline phosphatase) was 374 U/L, total bile acid 179.9 mumol/L, GGT (gamma-glutamyl transferase) 47U/L and aminotransferase levels were AST 34 U/L and ALT 42 U/L. Therefore, a diagnosis of alectinib-induced grade 4 hyperbilirubinemia (>10.0xULN if baseline was normal, Common Terminology Criteria for Adverse Events, v.5.0) was considered. Alectinib was held due to hepatotoxicity. Of note, he had no known liver metastases at baseline nor at follow-up scans. Assessment for viral hepatitis was unrevealing.
After hepatoprotective treatment comprising ursodeoxycholic acid, glycyrrhizin and glutathione was administered for one week, his bilirubin levels were still worsening, while AST and ALT levels remained similar. Drug-induced liver failure was diagnosed. Although artificial liver support or liver transplantation were both therapeutic choices for liver failure, considering he was a patient with advanced cancer, ALSS was an optimal choice. He received ALSS using a double plasma molecular absorption system (DPMAS) on June 5 and June 8, 2020, for the severe liver dysfunction. The total bilirubin continuously decreased after two courses of ALSS (Figure 3).
Alectinib was, therefore, discontinued for more than two months when a chest CT scan on August 5, 2020 revealed enlargement of lung lesions (Figure 2C and D) and overall disease progression. Ensartinib 225 mg once daily was given orally from August 29 as a second-line ALK TKI with initial tumor shrinkage after three months (Figure 2E and F) and stable disease overall by RECIST (Response Evaluation Criteria in Solid Tumors) criteria version 1.1. Toxicity of second-line ensartinib was grade 1 ALT and AST elevation and grade 1 skin rash, with no abnormality of bilirubin. The timeline of this patient is summarized in Figure 4.
Diagnoses of right lower lung adenocarcinoma, stage IV. CT mediastinum on Dec 17, 2019.