New onset myasthenia gravis in a patient with non small cell lung cancer treated with lorlatinib a novel anti-cancer agent

Neuromuscular Complications of Targeted Anticancer Agents: Can Tyrosine Kinase Inhibitors Induce Myasthenia Gravis? Getting Answers From a Case Report up to a Systematic Review

“…From the literature search, seven reports were identified (six case reports and one case series) that describe 12 cancer patients who developed MG after targeted therapy (15)(16)(17)(18)(19)(20)(21). The included articles were all retrospective studies, so the assessment of quality and risk of bias of analysis were performed using the 9-point Newcastle-Ottawa Scale (NOS) (Table 1).…”

“…The authors recognized an association between the onset of disorder and the ALK inhibition, since 5 years before any targeted therapy, AchR antibodies were negative while striational antibodies were positive (1:15,360). Given that the patient had no myasthenic symptoms over the previous 7 years of his NSCLC course, even while treated with older generation TKIs of the same class, lorlatinib seems to be the most possible cause of worsening neuromuscular symptoms (21).…”

“…Desai et al presented a heavily pretreated 56-year-old man with stage IV non-small cell lung adenocarcinoma, who developed MG being on partial response after 3 months of treatment with lorlatinib (PF-06463922, 100 mg daily) (21). Before this ALK TKI with high activity in patients harboring G1202R resistant mutation to crizotinib and ceritinib, the patient had initially received chemotherapy and, sequentially, crizotinib and ceritinib after the identification of ALK rearrangement.…”

“…Following the approval of imatinib in 2001, more than 40 TKIs have received hematological or oncological indications over the past 20 years, and many others are currently being tested in clinical and preclinical level, contributing to precision cancer medicine according to individual genetic alterations (14). Beyond their common toxicities (e.g., diarrhea, rash, hypertension, elevated transaminases, and fever), targeted agents have also been associated with few rare, sporadically described in the literature, but potentially severe, "off-target" sequelae, including myasthenic syndrome (15)(16)(17)(18)(19)(20)(21). Herein, we present the first patient with metastatic melanoma who developed anti-MuSK(+) MG after long-term administration of BRAF/MEK TKIs.…”

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.…”