Kahn-Pascual, Y.

Abstract Introduction: Abemaciclib is a cyclin-dependant kinase 4/6 inhibitor used to treat HR+/HER2- advanced or metastatic breast cancer with disease progression following endocrine or chemotherapy. In 2023, the FDA expanded its indication alongside endocrine therapy for early HR+/HER2- breast cancer with high risk of recurrence. We present a case of Abemaciclib induced pneumonitis to raise awareness of this rare complication in a relatively new treatment with growing use. Case Presentation: An 85 year old female with HFpEF, atrial fibrillation on Rivaroxaban and metastatic breast adenocarcinoma on Letrozole/Abemaciclib for three years, was admitted with non-productive cough, dyspnea and low-grade fever. On initial evaluation she was hypoxemic requiring 4L/min of oxygen, and in atrial fibrillation at 140bpm. Chest x-ray showed bilateral airspace and interstitial opacities with vascular congestion. Respiratory viral panel was negative, and labs showed lymphopenia, elevated BNP (5768pg/mL), elevated CRP (245mg/L) and ESR (135mm/h). Ceftriaxone and Azithromycin was started, and Letrozole/Abemaciclib held. After 72h, despite antibiotics, rate control and diuresis, her hypoxemia persisted. On reviewing prior PET-CT scans from her oncological monitoring, early mosaic attenuation in both lungs was noted. Chest CT was obtained and revealed diffuse ground-glass and reticular opacities with basilar apical gradient. Due to fragile respiratory status, bronchoscopy was deferred and induced-sputum obtained. Extensive testing was negative including autoimmune studies, serum beta-D-glucan and galactomannan, Histoplasma/Blastomyces, Pneumocystis jirovecii, AFB stain, sputum and blood cultures. With a negative workup and chest CT suggesting non-infectious pneumonitis, she was treated with Methylprednisolone for a Grade 4 Drug-Induced Interstitial Lung Disease (DIILD). Treatment resulted in rapid improvements, and she was eventually weaned off oxygen. She was discharged with prednisone taper and outpatient Pulmonology follow up with repeat CT in 6-8 weeks. Discussion: Abemaciclib is associated with severe, potentially fatal DIILD. In clinical trials MONARCH 1-3, 3.4% of patients had pneumonitis of any grade, 0.6% had Grade 3-4, and in 0.4% it was fatal. Many agencies including the FDA and MHRA (United Kingdom) released post-marketing surveillance warnings to raise awareness of this toxicity. Our case highlights an important differential when autoimmune or microbiological workup is negative, and the patient is not improving despite diuresis and antibiotics. PET-CT imaging is frequently done in these patients for oncological monitoring, and re-review of these prior scans during acute admissions can evaluate for early evidence of non-infectious pneumonitis. Prompt recognition, discontinuation of Abemaciclib and early steroid therapy can prevent progression to severe respiratory failure or death.