Alectinib (Alecensa)-induced reversible grade IV nephrotoxicity: a case report and review of the literature

Abstract

BackgroundLung cancer is among the top causes of cancer-related mortality in men and is the second most common cancer after breast cancer in women. There are approximately 234,030 new cases of lung cancer and 154,050 deaths from lung cancer in 2018 as per the latest American Cancer Society’s report. Alectinib, a more potent orally active tyrosine kinase inhibitor which was approved by the US Food & Drug Administration for anaplastic lymphoma kinase-positive lung adenocarcinoma, has been shown to have a reasonable safety profile when compared with other anaplastic lymphoma kinase-targeted therapy. As per research studies, grade 1 or 2 renal impairment has been reported but grade 4 renal toxicity due to alectinib has not been reported so far. We report a case of acute renal failure caused by alectinib which necessitated emergency dialysis. This is the first case report describing the severe renal toxicity of alectinib.Case presentationWe describe a case of 72-year-old Taiwanese man diagnosed with stage IV anaplastic lymphoma kinase-positive adenocarcinoma of the lung initially treated with crizotinib for over a year, which was switched to alectinib due to disease progression with brain metastasis. Within 6 weeks of starting alectinib, he developed acute renal failure needing emergency dialysis support. His renal failure was secondary to acute tubular necrosis and had a complete reversal within 7–10 days on withdrawing the medication. When he was re-challenged with alectinib, his creatinine started to worsen again which confirmed the renal toxicity of alectinib.ConclusionsThis case emphasizes the uncommon adverse effect of the anaplastic lymphoma kinase-targeted therapy alectinib causing acute renal failure manifesting as acute tubular necrosis. Recognition of alectinib nephropathy requires a thorough drug history and knowledge of risk factors that lessen its margin of safety at therapeutic ingestions. Frequent monitoring of renal functions and early nephrology referral significantly reduce the mortality and morbidity of these patients.

Acute kidney Injury due to Alectinib, an Anaplastic Lymphoma Kinase inhibitor

“…While the Anaplastic Lymphoma Kinase (ALK) inhibitor Crizotinib has been reported to be associated with acute kidney injury and chronic kidney disease, [1][2][3] the association with Alectinib is less well defined and merits further elucidation. [4][5][6] Alectinib is a second-generation highly selective oral Anaplastic Lymphoma Kinase (ALK) inhibitor approved by the FDA as first line therapy in ALK positive Non Small Cell Lung Carcinoma (NSCLC) and as second line therapy to Crizotinib resistant NSCLC. 6 Phase one studies of Alectinib in ALK-positive NSCLC reported increases in serum creatinine in 26% of participants, 6,7 and previous cases reported a temporal relationship between initiation of Alectinib and deterioration in kidney function without any other discernable cause, which improved with cessation of the agent.…”

“…6 Phase one studies of Alectinib in ALK-positive NSCLC reported increases in serum creatinine in 26% of participants, 6,7 and previous cases reported a temporal relationship between initiation of Alectinib and deterioration in kidney function without any other discernable cause, which improved with cessation of the agent. [4][5][6] The degree of kidney dysfunction varied across reported cases ranging from mild kidney injury to severe kidney injury requiring renal replacement therapy. 4 Nagai et al described a case of rapidly progressive glomerulonephritis following Alectinib initiation.…”

“…[4][5][6] The degree of kidney dysfunction varied across reported cases ranging from mild kidney injury to severe kidney injury requiring renal replacement therapy. 4 Nagai et al described a case of rapidly progressive glomerulonephritis following Alectinib initiation. 5 Kidney biopsy demonstrated glomerular crescents, and podocyte effacement in addition to tubulo-interstitial nephritis, tubular vacuolisation and tubulitis with the exclusion of immune complex disease by negative immunofluorescence.…”

“…4 The acute kidney injury was thought to be due to acute tubular necrosis and resolved within 7-10 days following Alectinib withdrawal. 4 Finally the authors attempted to re-challenge this patient with Alectinib and serum creatinine rose again suggesting causality. 4 A major challenge in the clinical management of these issues is the balance between treatment benefit elucidated from agents such as Alectinib in terms of reduced cancer progression and overall survival and the off-target side effects such as nephrotoxicity.…”

“…4 Finally the authors attempted to re-challenge this patient with Alectinib and serum creatinine rose again suggesting causality. 4 A major challenge in the clinical management of these issues is the balance between treatment benefit elucidated from agents such as Alectinib in terms of reduced cancer progression and overall survival and the off-target side effects such as nephrotoxicity. In our particular case, this individual was accruing a significant clinical benefit in terms of tumour burden response as assessed by radiological investigations, and hence we did not reduce the Alectinib dose or stop it since his kidney function stabilised at a lower level.…”