Palbociclib (Cyclin-Dependent Kinases CDK4 and CDK6 Selective Inhibitor) Induced Grade 3 Interstitial Pneumonitis

Introduction: In postmenopausal women, Palbociclib is a selective cyclin-dependent kinase CDK4 and CKD6 inhibitor to treat hormone receptor-positive metastatic breast cancer in combination with Letrozole (Aromatase Inhibitor). We describe a case presenting with the rare side effect of Palbociclib induced interstitial pneumonitis. Case report: A 70-year-old Caucasian female was admitted to the hospital with complaints of progressive dyspnea, dry cough, epistaxis, pleuritic chest pain over one month. Her past medical history was significant for stage IIIC (pT3N3) invasive ductal breast cancer (ER-positive/PR-negative/HER2-negative) status post left segmental mastectomy and axillary lymph node dissection 17 years ago. She received adjuvant chemotherapy, followed by Anastrozole, for five years. She had a metastatic recurrence to bones, liver, and lymph nodes, which was ER-positive/PR-negative/HER2-negative, and was started on Palbociclib and Letrozole by the oncology team four months before admission. Upon presentation, she was noted to have hypoxia requiring four liters of oxygen via nasal cannula. On examination, she was in severe respiratory distress and had bilateral crackles on lung auscultation. CT chest with contrast revealed no pulmonary embolism and bilateral patchy interstitial opacities. Her lab work showed neutropenia, lymphopenia, and anemia. She had a thorough evaluation for viral (including COVID-19), bacterial, and fungal infection, heart failure, and autoimmune disorders, which were negative. Although diagnostic bronchoscopy was offered, she declined the procedure. She continued to have worsening hypoxemia and required a high flow nasal cannula (FiO2 70% and 50 liters of flow) for moderate ARDS, which was presumed to be secondary to drug-induced pneumonitis. Given the pattern of lung injury on CT, the subacute nature of her symptoms, and initial non-invasive evaluation, it was felt that infectious pneumonia was unlikely. She was managed conservatively with discontinuation of Palbociclib, and IV steroids were initiated (20 mg dexamethasone daily). Over 14 days during the hospital stay, her hypoxemia largely resolved, and she was successfully discharged to a rehabilitation facility. On the day of discharge, she was discharged on PO Prednisone dose 0.5mg/kg for six weeks along with oral Bactrim full dose three times a week for PJP prophylaxis. Discussion: Palbociclib is commonly associated with neutropenia, anemia, thrombocytopenia, fatigue, infection, and gastrointestinal side effects. Rarely Palbociclib is associated with interstitial pneumonitis (incidence <1%) due to unknown mechanisms. The early identification of this side effect and treatment with immediate cessation of the drug and corticosteroids could be a life-saving measure, as is the case with our patient.