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.

Checkpoint inhibitors: literature review of new treatments for hepatocellular carcinoma.

OBJECTIVE: To systematically review the ongoing progress of effective treatment of advanced hepatocellular carcinoma (HCC), mainly focusing on immune checkpoint inhibitors (ICPI) as monotherapy and combination therapy. BACKGROUND: HCC in general has a poor prognosis; particularly in the advanced stage. For more than 10 years, the treatment with multikinase inhibitors was the first line treatment. Before the introduction of checkpoint inhibitors, very few treatments were available for patients with hepatocellular cancer in the advanced stage, especially in metastatic and unresectable disease. METHODS: We performed an extensive search of the ongoing and published clinical trials in the English written literature concerning of HCC with immune checkpoint inhibition when compared to first line chemotherapy. CONCLUSIONS: The treatment paradigm for advanced stage HCC has significantly changed recently with the introduction of immunotherapy; based on existing research, there is new era for HCC treatment which will positively affect the outcome in a malignancy that did not see therapy advancement for more than a decade. Monoclonal antibodies against programmed death ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1), such as nivolumab and pembrolizumab appear to be a promising therapeutic option in HCC. This review outlines immunotherapy that has been approved, and what inhibitors are under investigation for patients with advanced stage HCC.

A Rare Case of Epithelioid Malignant Peripheral Nerve Sheath Tumor Mimicking Malignant Melanoma.

Malignant peripheral nerve sheath tumors are rare soft tissue sarcomas that are often associated with neurofibromatosis type-1. These tumors share common immunohistochemistry findings which can make diagnosis difficult. We present the case of a woman who presented with a diagnosis of metastatic melanoma of the index finger of her left hand but was eventually diagnosed with primary epithelioid malignant peripheral nerve sheath tumor. We will be highlighting the diagnostic challenge of differentiating between these two very different malignancies.

Immune Checkpoint Inhibitors in Locally Advanced, Unresectable, and Metastatic Upper Gastrointestinal Malignancies.

BACKGROUND: Upper gastrointestinal (UGI) malignancies including esophageal, gastroesophageal junction (GEJ), and gastric cancers have a poor prognosis in the metastatic setting. Treatment with cytotoxic chemotherapy remains the treatment of choice in the first-line setting with the addition of trastuzumab, a monoclonal antibody against HER-2, if the tumor is HER2-positive. Before the era of checkpoint inhibitors, there were only few treatment options after failure of the first-line systemic therapy. METHODS: We extensively searched the English written literature for peer-reviewed manuscripts regarding the use of checkpoint inhibitors in advanced stage and metastatic UGI cancer. We also searched and reviewed ongoing clinical trials from Clinicaltrials.gov. RESULTS: Checkpoint inhibition is a promising therapeutic option in UGI cancers, which have overexpression of PD-L1, high mutation burden, or microsatellite instability. Checkpoint inhibitors that are being investigated or are approved in advanced UGI malignancies include PD-1 antibodies, nivolumab and pembrolizumab, PD-L1 antibody, avelumab, and CTLA-4 inhibitors, ipilimumab and tremelimumab. CONCLUSIONS: Based on recent and ongoing studies, eligible patients who have progressed beyond the first-line cytotoxic chemotherapy may benefit from immunotherapy. This review outlines the checkpoint inhibitors that are currently or previously being investigated for patients with metastatic UGI cancers.