CRA67 INTERSTITIAL PNEUMONITIS IN NON-SMALL CELL LUNG CANCER PATIENTS TREATED WITH LAZERTINIB, AMIVANTAMAB AND MINOCYCLINE

Up to 45% of patients with non-small cell lung cancer (NSCLC) in Malaysia harbour epidermal growth factor receptor mutation (EGFRm+). Monoclonal antibody Amivantamab and newer third-generation EGFR thyrosine-kinase inhibitors (EGFR-TKIs) Lazertinib are emerging therapies with promising progression-free survival; albeit with increased risks of overall severe (at least grade 3) adverse reactions (AEs) compared to Osimertinib. We report 2 patients with NSCLC who developed severe pneumonitis whilst on Lazertinib, Amivantamab and Minocycline. 

Case report 1

A 64-year-old lady, ex-smoker of 20 pack years, ECOG 1, was diagnosed with advanced stage NSCLC with EGFRm+. She received daily Lazertinib with scheduled intravenous Amivantamab together with minocycline and local emollient (to reduce dermatological AE) as part of a clinical trial. She presented with sudden-onset dyspnoea by the 2nd month of treatment necessitating non-invasive ventilation and subsequently intubation with mechanical ventilation. Features of diffuse alveolar damage were observed on computed tomography (CT). Her respiratory pathogen panel was positive for Pneumocystis Jirovecii. A diagnosis of drug-induced pneumonitis was made and she was commenced on intravenous methylprednisolone and broad-spectrum antibiotics. She succumbed on day 15 of hospitalization after a bout of ventilator-associated pneumonia. 

Case report 2

A 61-year-old gentleman, an ex-smoker of 40 pack years, received the same combination of EGFR-TKIs as part of a clinical trial. Like the previous case, he complained of worsening dyspnoea by the 2nd month of therapy and was intubated upon admission. Urgent CT showed ipsilateral lung disease progression with thrombosis and a crazy-paving appearance in the contralateral lung. Klebsiella pneumoniae DNA and multiple viruses RNA were detected on the respiratory pathogen panel. A clinical impression of drug-induced pneumonitis with pulmonary infection was made. He received intravenous methylprednisolone and broad-spectrum antibiotics but passed away on day 6 of hospitalization due to severe pneumonia with unresolved fast atrial fibrillation. 

Discussion

We report 2 cases of severe pneumonitis related to EGFR-TKI use with minocycline. In the MARIPOSA study, the incidence of pneumonitis did not differ between the Lazertinib- Amivantamab group and the Osimertinib group. (both at 3%, with grade 3 or higher events in 1% in each group). Both our patients received minocycline as per protocol not routinely practice in MARIPOSA study. Minocycline-induced pulmonary complications, from eosinophilic pneumonia to hypersensitivity pneumonitis have been reported in the literature. It remains unknown at this point as to whether minocycline use alone and/or a 3-drug combination is responsible for severe pneumonitis in our patients. Further observation and studies are eagerly needed to ensure a better clinical outcome.