Abstract INTRODUCTION Immunotherapy is an ever-evolving treatment modality for many sub-types of lung cancer, including non-small cell lung cancer (NSCLC) with selective mutations in epidermal growth factor receptor (EGFR). These NSCLC variants have limited treatment success with platinum-based chemotherapy regimens. Amivantamab, a bispecific monoclonal antibody that targets EGFR exon-20 insertions and MET receptors, is used to treat adults with NSCLC. Adverse effects and toxicities are common clinical concerns, and pneumonitis from amivantamab is estimated to occur in approximately 3% of patients. Grade ≥3 events often require multiple supportive therapies; plasmapheresis is not one such established therapy. CASE A 36-year-old female with stage IV lung adenocarcinoma undergoing immunotherapy with osimertinib and amivantamab (initiated four days prior due to disease progression) presented with new, acute hypoxic respiratory failure (AHRF) requiring 5L nasal cannula. She was admitted with continued corticosteroid therapy for suspected drug-induced pneumonitis with significantly increased, bilateral diffuse groundglass. Her AHRF worsened requiring high-flow nasal cannula (HFNC) and medical ICU admission (five days post-amivantamab). Hospital Day 3, nephrology was consulted and she received 1g/kg intravenous immunoglobulin. She further declined into Day 5 with increasing HFNC requirements; a five-day experimental course of plasmapheresis was initiated. Following four plasmapheresis sessions on Hospital Day 11, her AHRF was unchanged. On Day 13, she decompensated and was intubated. She had negative broad work-up for alternative etiology; Chest CT demonstrated worsening bilateral airspace disease. Fifth plasmapheresis session withheld due to lack of improvement; received infliximab Day 14. Following further complications (ventilator dyssynchrony, pneumomediastinum, pneumothorax, persistent 100% FiO2 requirement), patient transitioned to comfort care with palliative extubation on Day 19. DISCUSSION Risk factors for severe immunotherapy-related pneumonitis include NSCLC and combination systemic therapy - both were present here. Immune-suppressant therapy with corticosteroids and discontinuation of agent are first-line; use of immunomodulators (i.e., mycophenolate, cyclophosphamide, infliximab, IVIG) is recommended in steroid-refractory, severe cases. Plasmapheresis is a nonselective method of removing endogenous and exogenous antibodies from plasma. There is currently no evidence for use of plasmapheresis for pulmonary antibody-related adverse effects, though it is a second-line therapy for monoclonal antibody-related hyperviscosity syndromes. Early use (within 72-hours of administration) of plasmapheresis has been effective at removing substantial amounts of monoclonal antibodies (e.g., rituximab) and reducing therapeutic exposure. This was a grade 5 drug-induced pneumonitis event with experimental application of plasmapheresis following failure of recommended management. Earlier initiation may have optimized theoretical therapeutic response; additional clinical studies are needed. This abstract is funded by: None
Henderson et al. (Fri,) studied this question.