Pneumonitis and cellular immunodeficiency triggered by the CDK 4/6 inhibitor Abemaciclib

Breast cancer is the second most common cancer amongst women in the United States following non-melanoma skin cancer. There were an estimated 276,480 new cases and 42,170 deaths in 2020. The lifetime risk for developing breast cancer in females is about 13%. In the United States this year approximately 284,200 people out of which 281,550 women and 2,650 men, will be diagnosed with invasive breast cancer. In recent years, treatment options with novel mechanisms have emerged. Cyclin dependent kinase (CDK) 4/6 inhibitors, namely palbociclib, ribociclib and abemaciclib, are relatively new targeted therapies for treating breast cancers express estrogen receptors (ER) and/or progesterone receptors (PR). CDKs are important regulatory enzymes in cell cycle transitions and cell division. Selective inhibition of CDK4/6 causes cell cycle to arrest in the G1 phase, resulting in reduced cell viability and tumor response. Abemaciclib is the only one approved as monotherapy. Palbociclib and ribociclib must be used as adjunctive therapy to endocrine therapy such as tamoxifen, aromatase inhibitors or fulvestrant. Common side effects include neutropenia, thrombocytopenia, fatigue, nausea, and vomiting. A black box warning for all CDK inhibitors is a rare but possibly fatal severe inflammation of the lungs, called pneumonitis. We present a fatal case of severe pneumonitis with superimposed fungal respiratory infection in the setting of hypogammaglobulinemia in a 65-year-old female with metastatic ER and PR positive, human epidermal growth factor receptor 2 (HER-2) negative breast cancer who received abemaciclib.