Fatal Tumour Lysis Syndrome Induced by Brigatinib in a Lung Adenocarcinoma Patient Treated With Sequential ALK Inhibitors: A Case Report

Abstract

Tumour lysis syndrome (TLS) represents a group of fatal metabolic derangements resulting from the rapid breakdown of tumour cells. TLS typically occurs soon after the administration of chemotherapy in haematologic malignancies but is rarely observed in solid tumours. Here, we report a case of brigatinib-induced TLS after treatment with sequential anaplastic lymphoma kinase (ALK) inhibitors in a patient with advanced ALK-rearranged lung adenocarcinoma. The patient was treated sequentially with crizotinib, alectinib, and ensartinib. High-throughput molecular profiling after disease progression indicated that brigatinib may overcome ALK resistance mutations, so the patient was administered brigatinib as the fourth-line treatment. After 22 days of therapy, he developed oliguria, fever, and progressive dyspnoea. Clinical manifestations and laboratory findings met the diagnostic criteria for TLS. The significant decrease in the abundance of ALK mutations in plasma indicated a therapeutic response at the molecular level. Consequently, the diagnosis of brigatinib-induced TLS was established. To the best of our knowledge, this is the first case of TLS induced by sequential targeted therapy in non-small cell lung cancer. With the extensive application of sequential therapy with more potent next-generation targeted therapeutic drugs, special attention should be given to this rare but severe complication.

Keywords: acute kidney injury; brigatinib; case report; non-small cell lung cancer; targeted therapy; tumour lysis syndrome.

FIGURE 1

The Clinical course of the disease, treatment history, and response evaluation. (A) Timeline of treatment and molecular profiling based on tissue and liquid biopsies. (B) Duration of disease response evaluated by CT and PET/CT. CT, computed tomography; PET/CT, positron-emission tomography/computed tomography.

FIGURE 2

An overview of somatic mutation profiles within tissue and liquid biopsies using the next-generation sequencing technique. (A) Each row represents one individual biopsy sample, and each column represents one somatic genetic alteration. (B) Dynamic changes in the gene abundance of plasma ctDNA. Solid lines represent ALK mutations, and dashed lines represent concomitant mutations. ctDNA, circulating tumour DNA.