Crizotinib-induced osteitis mimicking bone metastasis in a stage IV ALK-rearranged NSCLC patient: a case report

Abstract

Background: Targeted therapies are a standard of care for first-line treatment of Anaplastic lymphoma kinase (ALK)rearranged non small cell lung cancer (NSCLC). Giving the rapid pace of drug discovery and development in this area, reporting of adverse effects of ALK inhibitors is crucial. Here, we report a case of osteitis induced by an ALK inhibitor mimicking bone metastasis, a previously undescribed side effect of crizotinib. Case presentation: A 31-year-old woman with stage IV ALK-rearranged NSCLC presented with back pain after 3 months of crizotinib treatment. Diagnostic work-up showed osteitis on the 4th and 5th thoracic vertebrae, anterior soft tissue infiltration and epiduritis, without any sign of infection. Spinal cord decompression, histological removal and osteosynthesis were performed. Histologic examination showed necrosis with abundant peripheral neutrophils, no microorganism nor malignant cell. Symptoms and Computarized Tomography-abnormalities rapidly diseappeared after crizotinib withdrawal and did not recur after ceritinib onset. Conclusions: This is the first report of crizotinib-induced osteitis. Crizotinib differs from other ALK inhibitors as it targets other kinases as well, which may have been responsible for the osteitis. Crizotinib can induce rapidly extensive osteitis, which can mimic tumor progression.

Insights into the antimicrobial effects of ceritinib against Staphylococcus aureus in vitro and in vivo by cell membrane disruption

“…In its dosage as an antimicrobial agent, we observed that the CERI-treated group showed significantly lower WBC counts than the vehicle group, which could be due to its ability to suppress the release of neutrophils (Guisier et al 2020 ). However, we found no indiscriminate variation in RBC, PLT, or HGB (Fig.…”

Postmarketing safety of anaplastic lymphoma kinase (ALK) inhibitors: an analysis of the FDA Adverse Event Reporting System (FAERS)

“…11 Treatment with ALK inhibitors is usually well tolerated; however, there are common class adverse events such as nausea, vomiting, diarrhea, pneumonitis, and cardiac toxicity. 12 Some less common adverse events have been reported as well including rectal perforation, 13 cataract, macular edema or blindness, 14,15 osteitis, 16 ventricular fibrillation, 17,18 pulmonary arterial hypertension, 19 pancreatitis, 20 cholestasis, 21 alopecia, 22 proteinuria, 23 myasthenia gravis, 24 toxic epidermal necrolysis, 25 sarcoid-like reaction, 26 and photosensitivity. 27 Treatment discontinuation due to adverse events among different ALK inhibitors were as follow: 12% with crizotinib as in the PROFILE 1014 trial, 28 5% with ceritinib as in the ASCEND 4 trial, 29 11% with alectinib as in the ALEX trial, 30 12% with brigatinib as in the ALTA-1L trial, 10 and 7% with lorlatinib as in the CROWN trial.…”

“…Treatment with ALK inhibitors is usually well tolerated; however, there are common class adverse events such as nausea, vomiting, diarrhea, pneumonitis, and cardiac toxicity. 12 Some less common adverse events have been reported as well including rectal perforation, 13 cataract, macular edema or blindness, 14 , 15 osteitis, 16 ventricular fibrillation, 17 , 18 pulmonary arterial hypertension, 19 pancreatitis, 20 cholestasis, 21 alopecia, 22 proteinuria, 23 myasthenia gravis, 24 toxic epidermal necrolysis, 25 sarcoid-like reaction, 26 and photosensitivity. 27 …”