Lambert Eaton Myasthenic Syndrome (LEMS) Secondary to Atezolizumab in a Patient with Squamous Cell Carcinoma of the Lung

Introduction: Lambert Eaton myasthenic syndrome (LEMS) is an autoimmune disorder in which autoantibodies are produced against pre-synaptic voltage gated calcium channels, interfering with the normal pre-synaptic calcium influx required for acetylcholine release. Consequently, nerve to muscle conduction is disrupted, resulting in muscle weakness. It has often been described as a paraneoplastic syndrome, usually in association with small cell lung cancer. Here, we describe a case of LEMS in a patient with squamous cell lung cancer (SCC) treated with the immunotherapy atezolizumab.

Case presentation: A 67-year-old male with an extensive smoking history of forty pack years underwent routine lung cancer screening computed tomography (CT) which showed a 4.9 x 5.6 cm right lower lung mass. He underwent workup including CT chest, abdomen and pelvis, magnetic resonance imaging (MRI) of brain and bronchoscopy with biopsy which confirmed squamous cell carcinoma of the right lung, stage IIIA. He underwent right lung lobectomy with thoracic lymphadenectomy, received four cycles of cisplatin/ taxotere and was started on maintenance therapy with atezolizumab. His cancer was in complete remission, with no evidence of recurrence on subsequent computed tomography (CT) imaging. A week after his fourth cycle of atezolizumab, he presented to the emergency room (ER) with diplopia, facial droop and neck weakness with difficulty holding his neck up. He also experienced significant dyspnea on lying flat. He was hemodynamically stable. Physical exam was significant for mild right sided facial droop, diplopia in all fields of vision, flexion of neck and 4/5 motor power in bilateral upper and lower extremities. CT angiogram of the head showed no evidence of any vascular pathology or acute stroke. MRI of the brain demonstrated no evidence of intracranial metastasis. Per neurology opinion, patient's neurological findings were consistent with a myasthenic syndrome in the setting of immunotherapy with atezolizumab for lung cancer. Myasthenia workup including acetylcholine receptor antibodies (AChR AB), anti-muscle-specific kinase (Anti-MuSK) antibodies, creatine kinase (CK) and voltage gated calcium channels (VGCC) antibodies were sent. In the meantime, patient was started on oral pyridostigmine 60 mg three times a day and prednisone 40 mg twice a day. Given his inadequate response to pyridostigmine and steroids, a decision was made to start the patient on plasmapheresis. His VGCC antibodies turned out to be positive, consistent with Lambert-Eaton syndrome. His vital capacity (VC) and negative inspiratory forces (NIF) were constantly monitored on plasmapheresis sessions. He received a total of five plasmapheresis treatments with remarkable improvement in his weakness, also evident by improvement in VC and NIF. Patient was discharged on a steroid taper and his atezolizumab was stopped permanently.

Discussion: Lambert Eaton myasthenic syndrome is rare complication of atezolizumab. A few case reports exist where it has been described in association with other immunotherapy drugs for lung cancer such as nivolumab, ipilimumab but rarely with atezolizumab. In these case reports, it has been associated with immunotherapy in small cell lung cancer (SCLC), where it can be a paraneoplastic syndrome of SCLC or an adverse effect of immunotherapy or both. Almost 40-60% of patients diagnosed with LEMS are found to have SCLC. Our case is unique since LEMS occurred as a result of immunotherapy with atezolizumab in a patient with squamous cell carcinoma (SCC) of the lung. Moreover, the patient was in remission for his SCC, with no evidence of recurrent cancer on imaging.

Conclusion: Atezolizumab treatment can result in the development of autoimmune conditions such as LEMS which could be life-threatening if not recognized and treated promptly.

No relevant conflicts of interest to declare.