A Comprehensive Review of Immunotherapy Clinical Trials for Metastatic Urothelial Carcinoma: Immune Checkpoint Inhibitors Alone or in Combination, Novel Antibodies, Cellular Therapies, and Vaccines.

Urothelial cancer is an immune-responsive cancer, but only a subset of patients benefits from immune checkpoint inhibition. Currently, single-agent immune checkpoint inhibitors (ICIs) and the combination of pembrolizumab with the antibody-drug conjugate enfortumab vedotin are approved to treat patients with metastatic UC (mUC). Approval of first-line nivolumab in combination with gemcitabine and cisplatin is expected imminently. Many treatment approaches are being investigated to better harness the immune system to fight mUC. In this review, we summarize the landmark clinical trials of ICIs that led to their incorporation into the current standard of care for mUC. We further discuss recent and ongoing clinical trials in mUC, which are investigating ICIs in combination with other agents, including chemotherapy, antibody-drug conjugates, tyrosine kinase inhibitors, and novel antibodies. Lastly, we review novel approaches utilizing bispecific antibodies, cellular therapies, and vaccines. The landscape of immunotherapy for mUC is rapidly evolving and will hopefully lead to better outcomes for patients.

An Unusual Presentation of Multiple Myeloma: A 71-Year-Old Female With a Single Lytic Lesion of Her Appendicular Skeleton.

Multiple myeloma is a devastating illness with a hallmark of end-organ damage. The clinical presentation of multiple myeloma often includes the involvement of CRAB (hypercalcemia, renal failure, anemia, bone lesions) symptoms. We present a case of a patient who did not exhibit the typical presentation of multiple myeloma making her case unique and her diagnosis more difficult. In addition to the CRAB criteria, typical symptomatology includes constipation, pain, fatigue, and peripheral sensory issues. The purpose of this case report is to bring awareness to both multiple myeloma and this particular presentation. The patient is a 71-year-old female with a past medical history of hypertension, hypothyroidism, and rheumatoid arthritis who presented with a chief complaint of right shoulder pain. The patient's initial labs were significant for a total protein of 9.3, albumin of 3.4, corrected calcium of 9.3, hemoglobin 10.6 (with baseline near 11-12), and creatinine of 1.0 (baseline of 1.0). The patient's right upper extremity X-rays were significant for a right humeral fracture. The patient had a serum kappa/lambda ratio of 15.94. Bone marrow biopsy revealed 50% kappa-restricted cells, consistent with a diagnosis of multiple myeloma. The patient's subsequent bone survey and CT scan were negative for any additional lesions. The patient had subsequent radiation therapy followed by maintenance therapy with bortezomib, lenalidomide, and dexamethasone with improvement in her symptoms. MM is a complex pathophysiological disease and equally as complex in diagnosis as the presentation is varied and sometimes obscure as noted in the case presented here. Although bone lytic lesions are part of the CRAB criteria, it is rare for them to present in patients with MM in an isolated manner with no corresponding lab abnormalities. With this case, we aim to shed light upon an atypical presentation of MM, notably one that solely involves a pathological fracture in a non-axial distribution.