Durable Complete Remission With Combination of Stereotactic Body Radiation Therapy (SBRT) and Talimogene Laherparepvec (TVEC) Followed by Ipilimumab in Refractory Metastatic Melanoma.

Metastatic melanoma refractory to checkpoint inhibitors is a challenging clinical scenario. We present the case of a patient who was refractory to standard of care but was able to achieve a durable complete remission with the combination of stereotactic body radiation therapy (SBRT), talimogene laherparepvec (TVEC), and ipilimumab.

Case report: response to the ERK1/2 inhibitor ulixertinib in BRAF D594G cutaneous melanoma.

Melanoma is characterized by oncogenic mutations in pathways regulating cell growth, proliferation, and metabolism. Greater than 80% of primary melanoma cases harbor aberrant activation of the mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) pathway, with oncogenic mutations in BRAF, most notably BRAF V600E, being the most common. Significant progress has been made in BRAF-mutant melanoma using BRAF and MEK inhibitors; however, non-V600 BRAF mutations remain a challenge with limited treatment options. We report the case of an individual diagnosed with stage III BRAF D594G-mutant melanoma who experienced an extraordinary response to the ERK1/2 inhibitor ulixertinib as fourth-line therapy. Ulixertinib was obtained via an intermediate expanded access protocol with unique flexibility to permit both single-agent and combination treatments, dose adjustments, breaks in treatment to undergo surgery, and long-term preventive treatment following surgical resection offering this patient the potential for curative treatment.

Evaluation of thrombophilia testing in the inpatient setting: A single institution retrospective review.

BACKGROUND: Thrombophilia workup is typically inappropriate in the inpatient setting as testing may be skewed by anticoagulation, acute thrombosis, or acute illness. OBJECTIVE: To determine adherence of inpatient thrombophilia testing with institutional guidelines. PATIENTS AND METHODS: A retrospective study to evaluate thrombophilia testing practices of adult patients who were admitted to Lehigh Valley Hospital at Cedar Crest with either venous thromboembolism or ischemic stroke in 2019. Testing included inherited and acquired thrombophilia. Patient charts were individually reviewed for three measured outcomes: 1) the number of appropriate thrombophilia testing in the inpatient setting; 2) the indications used for thrombophilia testing; 3) the proportion of positive thrombophilia tests with change in clinical management. RESULTS: 201 patients were included in our study. 26 patients (13%) were tested appropriately in accordance with institution guidelines and 175 (87%) patients were tested inappropriately. The most common reason for the inappropriate testing was testing during acute thrombosis. 28 of the 201 patients had positive thrombophilia tests, but the reviewers only noted 7 patients with change in clinical management-involving anticoagulation change. CONCLUSION: Our study revealed that a majority of inpatient thrombophilia testing did not follow institutional guidelines for appropriate testing and did not change patient management. These thrombophilia tests are often overutilized and have minimal clinical utility in the inpatient setting.

Thrombotic Thrombocytopenic Purpura Induced by Immune Checkpoint Inhibitiors: A Case Report and Review of the Literature.

In recent years, the role of immune checkpoint inhibitors (ICI) in cancer treatment has rapidly expanded. In randomized clinical trials, these agents have demonstrated clinical efficacy in extending survival and increasing response rates. Immune-related adverse effects (irAEs) involving various organs have been frequently narrated. Herein, we present a case report of thrombotic thrombocytopenic purpura (TTP) as a rare side effect of nivolumab, plus ipilimumab, in the treatment of metastatic renal cell carcinoma (RCC). A review of the literature for other case reports of TTP during treatment with ICIs was also performed. Our aim is to elucidate the significance of early recognition of this rare adverse effect in patients being treated with this relatively newer class of medications.

Isolated Left Ventricular Metastasis from Renal Cell Carcinoma: Diagnostic and Therapeutic Dilemma.

BACKGROUND: The treatment of metastatic renal cell carcinoma (RCC) has been radically changed by the advent of tyrosine kinase inhibitors (TKIs). However, few reports have described their role in cardiac metastases. We present a case of a left ventricular metastasis from RCC that was managed with pazopanib therapy. CASE REPORT: A 74-year-old male with stage I RCC underwent right nephrectomy in 2004 and right lung metastasis resection in 2009. He was well till March 2016, when he presented with chest pain. Cardiac catheterization revealed a highly vascular mass in the apex. Cardiac magnetic resonance imaging revealed a left ventricular mass with full-thickness involvement of the myocardium, and the open cardiac biopsy was consistent with metastatic RCC. The patient was initially treated with pazopanib with response but later developed therapy-related side effects, and the dose was reduced. Due to tumor progression, he is currently on nivolumab instead and is stable. CONCLUSION: RCC with cardiac metastasis poses unique challenges with regard to diagnosis as well as treatment. The use of TKI therapy is associated with cardiotoxicity and has not been adequately studied in cardiac metastasis. Choosing the right treatment for this subgroup of patients continues to pose an ongoing dilemma.

Acute Brachial Artery Occlusion in an Elderly Patient With Acute Myocardial Ischemia.

We present a case of left upper extremity paresis secondary to acute brachial artery occlusion in an elderly female with active non-ST segment elevation myocardial ischemia (NSTEMI) in the setting of paroxysmal atrial fibrillation. The patient was initially suspected to have a cerebrovascular attack (CVA); however, computed tomography (CT) head was negative for acute stroke. The diagnosis was confirmed by computed tomographic angiography (CTA) of the upper extremity, confirming the diagnosis of acute left brachial artery occlusion. In evaluating a patient with concern for acute stroke with atypical presentation, it is essential to obtain a complete history and perform a rapid and thorough examination. Acute limb ischemia (ALI) should be considered in the differential diagnosis of CVA with atypical presentation.

Acquired von Willebrand Syndrome in IgM Monoclonal Gammopathy as the Presentation of Lymphoplasmacytic Lymphoma.

Acquired von Willebrand syndrome (AVWS) is an increasingly recognized entity with numerous potential underlying etiologies. Most commonly implicated are lymphoproliferative, myeloproliferative, cardiovascular, and autoimmune disorders. Unlike inherited von Willebrand disease (vWD), AVWS tends to present at an older age and without a family history of vWD. Treatment is directed at the underlying etiology if one is uncovered, as well as treatment and prevention of bleeding. Here, we present a rare case of AVWS secondary to Waldenström macroglobulinemia which went unrecognized for several years but resolved promptly with treatment. The potential mechanisms of AVWS secondary to monoclonal gammopathies are discussed as well as strategies to treat and prevent bleeding in these patients.