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.

A Novel ALK Gene Mutation and Its Response to Second-Generation TKIs: a Case Report and Literature Review

“…However, for the present case, the response to ensartinib only lasted for one month, which indicated that E803Q might be resistant to ensartinib. Similarly, for the case reported by Wang et al, ensartinib only achieved SD for patients who relapsed from alectinb treatment with multiple secondary mutations, including L1196M, G1269A, F1174L, and V1180L, and the PFS for ensartinib was only four months 17 . It has been demonstrated that the V1180L mutation is still sensitive to ceritinib in preclinical studies 11,16 .…”

Afatinib-Induced Tumor Lysis Syndrome in Pulmonary Adenocarcinoma: A Case Report and Literature Review

“…We have identified seven previous reports of the occurrence of TLS in patients with pulmonary adenocarcinoma [9,10,[16][17][18][19][20]. All seven patients had metastatic disease: four had liver metastases and four had lymph node involvement.…”

“…The occurrence of TLS in association with targeted therapy is very rare. Furthermore, few cases of TLS have been identified in patients with pulmonary adenocarcinoma receiving targeted agents, such as EGFR-TKIs and ALK-TKIs [9,10]. Only two cases of TLS have been identified in patients with pulmonary adenocarcinoma receiving targeted therapy.…”

“…Only two cases of TLS have been identified in patients with pulmonary adenocarcinoma receiving targeted therapy. The first case was induced by gefitinib, a first-generation EGFR-TKI [9]; the other case was associated with brigatinib, an ALK-TKI [10]. To the best of our knowledge, this is the first case of afatinib-induced TLS in pulmonary adenocarcinoma.…”

“…Most reports have described patients with small cell lung cancer (SCLC), whereas some reports have described patients with non-small cell lung cancer (NSCLC). Additionally, there have been few reports of pulmonary adenocarcinoma treatment with targeted agents, including epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and anaplastic lymphoma kinase tyrosine kinase inhibitor (ALK-TKI) [9,10].…”