Atezolizumab-Induced Lambert-Eaton Myasthenic Syndrome in a Patient With Small-Cell Lung Cancer.

The case of a 70-year-old man who developed Lambert-Eaton myasthenic syndrome (LEMS) while receiving atezolizumab treatment for extensive-stage small-cell lung cancer (SCLC) is presented. He started receiving maintenance immunotherapy with atezolizumab following four cycles of combination therapy with atezolizumab, carboplatin, and etoposide. After five cycles of maintenance atezolizumab therapy, he complained of muscle weakness in the lower limbs and fatigue. Electromyographic findings and positive results for anti-P/Q-type voltage-gated calcium channel antibody made a diagnosis of LEMS. Based on the onset time of LEMS and the state of his underlying cancer at the time of the appearance of neurological symptoms, he was diagnosed with LEMS as an immune-related adverse event (irAE) induced by atezolizumab. After discontinuing atezolizumab treatment and initiating combination therapy with steroid pulse plus intravenous immunoglobulin, his neurological symptoms improved. Although 18 months have passed since the discontinuation of atezolizumab treatment, there has been neither recurrence of neurological symptoms nor a progression of his cancer without salvage chemotherapy. This is a rare case of LEMS as a neurological irAE induced by atezolizumab. Clinicians must be aware of the potential for LEMS to develop in SCLC patients taking atezolizumab treatment.

Alveolar Hemorrhage Caused by the Combination of Immune Checkpoint Inhibitors (ICIs) and Angiogenesis Inhibitors: The Underlying Long-Term Vascular Endothelial Growth Factor (VEGF) Inhibition.

The combination of immune checkpoint inhibitors (ICIs) and other anticancer agents is the standard of care for various cancers. Bevacizumab, an anti-angiogenesis inhibitor, causes serious adverse events such as pulmonary hemorrhage (PH). Here, we present a case of drug-induced diffuse alveolar hemorrhage (DAH), an adverse event, in a patient with hepatocellular carcinoma who was treated with a combination of ICIs and anti-angiogenesis inhibitors after long-term use of lenvatinib, which inhibits vascular endothelial growth factor (VEGF). An 85-year-old man with hepatocellular carcinoma initially received lenvatinib, a multi-kinase inhibitor, but the drug was later switched to bevacizumab-atezolizumab combination therapy owing to disease progression. After five cycles, he developed dyspnea and diffuse ground-glass opacities, which improved with discontinuation of the combination therapy and initiation of steroid pulse therapy. Our case findings indicate that both ICIs and anti-angiogenesis inhibitors cause drug-induced DAH, and their combination may increase the severity of DAH. Moreover, long-term VEGF inhibition may induce the development of DAH. Clinicians need to be aware that long-term VEGF inhibition may be associated with DAH and should consider the risk management of such adverse events while using this combination therapy.

Radical Resection for Second EGFR-mutated Primary Lung Cancer Following Immune Checkpoint Inhibitor Monotherapy for Stage IV Lung Adenocarcinoma.

A 78-year-old woman with multiple lung nodules, epithelial growth factor receptor (EGFR) exon 20 insertion mutations, and diagnosed with advanced lung adenocarcinoma (cT4N3M1a, stage IVA), was referred to our hospital. She received immune checkpoint inhibitor (ICI) therapy. The therapy showed remarkable antitumor effects; only a single nodule remained in the right upper lobe. The nodule was diagnosed as adenocarcinoma through a biopsy. We subsequently performed right upper lobectomy for multiple primary lung cancer (MPLC). The surgical specimen contained EGFR exon 19 deletion mutations and not exon 20 insertion mutations.