Abstract Introduction Chemotherapy-induced pneumonitis (CIP) is a complication of many cancer therapies, including medications known as antibody-drug conjugates (ADCs). Mirvetuximab soravtansine-gynx (MIRV) is an ADC targeting folate receptor alpha (FRα) that was fully approved by the FDA in 2024 and is used in the treatment of platinum-resistant, FRα-positive ovarian, fallopian tube, or peritoneal cancer. Among MIRV treated patients, pneumonitis has been reported in up to 10-24% based on trial data. Using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE), CIP is graded from 1 (mild) to 5 (fatal). While most reported cases of pneumonitis in patients receiving MIRV are mild, grade 4 events are exceedingly rare, occurring in only 0.1% of patients. We present a rare case of grade 4 MIRV-induced pneumonitis. Case A 63-year-old woman with high-grade ovarian cancer, having completed 15 cycles of MIRV, presented with progressive dyspnea over several weeks. On arrival, she was hypoxic with an SpO2 of 83% on room air and tachypneic with a respiratory rate of 30. Given her respiratory distress, she required BiPAP with an FiO2 of 70%. Arterial blood gas at that time showed pH 7.32, pCO2 40, pO2 69. Due to her hypoxemia and increased work of breathing, she was emergently intubated and underwent bronchoscopy. CT imaging revealed diffuse bilateral consolidations and reticular opacities (Fig 1). Laboratory studies including CBC, CMP were unremarkable, and lactic acid was 2.1 mmol/L. She was started on IV methylprednisolone (1 mg/kg) for suspected grade 4 MIRV-induced pneumonitis. MIRV was permanently discontinued. Infectious workup remained negative throughout her hospitalization. She was intubated for 10 days but gradually improved, requiring only 2L nasal cannula at discharge. Discussion While MIRV carries a black box warning for ocular toxicity, it has no formal warning for pneumonitis. MIRV is composed of an FRα-directed antibody linked to DM4, a microtubule inhibitor. One study analyzing the corneal deposits in the anterior corneal stroma elucidated a pathway: FRα is not present in the cornea or normal lung tissue and DM4’s anti-mitotic effects may be responsible for injury. However, other studies have found no correlation between ADC staining intensity and incidence of interstitial lung disease (ILD). Additional risk factors for MIRV-associated pneumonitis include prior mediastinal lymphadenopathy or pleural effusions. Although this patient responded to corticosteroids, other potential therapies include tocilizumab, infliximab, mycophenolate, IVIG, and cyclophosphamide. Prompt recognition and early corticosteroid treatment remain critical for improving outcomes. This abstract is funded by: None
Rice et al. (Fri,) studied this question.