Abstract Introduction Microsatellite instability-high (MSI-H) non-small cell lung cancer (NSCLC) is rare with approximately 0.6-0.8% of lung cancer cases. MSI-H is due to deficient DNA mismatch repair (dMMR), resulting in a hypermutated phenotype with high neoantigen load. Although well-established in colorectal and endometrial cancers, it is rare among lung cancers. MSI-H is a predictive biomarker for immune checkpoint inhibitor (ICI) response in lung cancer. We report a rare case of MSI-H metastatic lung adenocarcinoma initiated on dual ICI therapy. Case Presentation 76-year-old lady nonsmoker with medical history of osteoarthritis, CVA, hypertension, mild dementia presented with shortness of breath with minimum exertion and left-sided chest pain for 2 weeks. CT with contrast of the chest showed a very large left-sided pleural effusion causing complete collapse of the left lung and right sided mediastinal shift, pleural nodular thickening and enhancement and right basilar nodularity. She underwent thoracentesis in the hospital and 1 L of clear yellow exudative fluid was removed. Cytology confirmed non-small cell carcinoma consistent with adenocarcinoma. Tumor cells were positive for Ber-EP4, MOC31 and CK7and weak positive for TTF1. CT scan of the abdomen and pelvis with contrast showed some epicardial nodularity. PET- CT of the whole body had mild diffuse uptake within the left pleura suspicious for neoplasm and no evidence of metastatic disease in the abdomen and pelvis. Pathology/cytology showed non-small cell lung carcinoma, adenocarcinoma stage IV with pleural involvement which was PD L1 negative. Quadrant fluid biopsy resulted MSI high and Tumor mutation burden (TMB) 42.6 mut/Mb. Echo was normal with ejection fraction of 60-65%. The patient was discharged from the hospital after having left-sided PleurX catheter placed which showed minimal drainage after 5 weeks of discharge. The Patient’s clinical stability enabled comprehensive genetic testing, which despite requiring additional time for results, offered valuable insights into the tumor biology and informed a more targeted immunotherapy approach. Patient was started on immunotherapeutic agents- Nivolumab and ipilimumab. Discussion MSI-H NSCLC is rare and poses diagnostic and therapeutic challenges, particularly in PD-L1-negative tumors. MSI-H confers high sensitivity to ICIs due to abundant neoantigen formation and enhanced immune recognition. Evidence suggests dual ICI therapy may provide durable clinical response in MSI-H NSCLC irrespective of PD-L1 status. MSI testing may help identify this small subgroup. This case also highlights the importance of comprehensive genetic testing, which can help identify candidates for targeted immunotherapy over conventional chemotherapy, potentially improving efficacy and reducing treatment related toxicity This abstract is funded by: None
Poojary et al. (Fri,) studied this question.