Citations

Abstract Glioblastoma (GBM) is the most prevalent malignant tumor of the central nervous system. The prognosis of GBM is grim, with a median overall survival of 14.6 months and only 6.9% of patients surviving 5 years after the initial diagnosis. Despite poor outcomes, standard therapy of surgical resection, radiotherapy, chemotherapy, and tumor-treating fields has remained largely unchanged. The introduction of immune checkpoint inhibitors (ICI) has been a paradigm shift in oncology, with efficacy across a broad spectrum of cancer types. Nonetheless, investigations of ICIs in both newly diagnosed and recurrent GBM have thus far been disappointing. This lack of clinical benefit has been largely attributed to the highly immunosuppressive nature of GBM. However, immunotherapy still holds promise for the treatment of GBM, with combinatorial strategies offering hope for potentially overcoming these current limitations. In this review, we discuss the outcomes of clinical trials employing ICIs in patients with GBM. Afterward, we review ICI combination strategies and how these combinations may overcome the immunosuppressive microenvironment of GBM in the context of preclinical/clinical evidence and ongoing clinical trials.

AbstractWe present a case of a 60‐year‐old male who was found to be in atrial fibrillation during routine evaluation. Anticoagulation was initiated for 36 h and he was referred for TEE‐guided electrical cardioversion. There was no thrombus identified in the left atrial appendage, however, the appendage was large and had a tongue‐like accessory lobe along with spontaneous contrast in the left atrium and its appendage. TEE probe was not withdrawn, patient underwent successful cardioversion with 200 joules and developed a marked increase in left atrial and left atrial appendage spontaneous contrast along with the development of tear drop shaped thrombus in the left atrial appendage immediately after cardioversion, which rapidly became more dense. There was an associated marked decrease in appendage velocities. Patient was hospitalized to initiate low molecular weight heparin. This case highlights the need for vigilance in patients with an unknown duration of atrial fibrillation, who have received a short duration of anticoagulant therapy and who have adverse appendage anatomy as thrombus may develop immediately after cardioversion despite anticoagulation.

We present a case of a 60 year old male who found to be in atrial fibrillation during routine evaluation. Anticoagulation was initiated for 36 hours and he was referred for TEE guided electrical cardioversion. There was no thrombus identified in the left atrial appendage, however the appendage was large and had a tongue like accessory lobe along with spontanous contrast on the left atrium and its appendage. TEE probe was not withdrawn, patient underwent successful cardioversion with 200 joules and developed a thrombus in the left atrial appendage immediately after cardioversion, which rapidly became more dense. There was an associated marked decrease in appendage velocities. Patient was hospitalized to initiate low molecular weight heparin. This case highlights the need for vigilance in patients with unknown duration of atrial fibrillation, who have received a short duration of anticoagulant therapy and who have adverse appendage anatomy as thrombus may develop immediately after cardioversion despite anticoagulation.

Abstract Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454‐489.

Glembatumumab vedotin (CDX-011, GV) is a fully human Immunoglobulin G2 monoclonal antibody directed against glycoprotein NMB coupled via a peptide linker to monomethyl auristatin E (MMAE), a potent cytotoxic microtubule inhibitor. This phase II study evaluated the overall response rate and safety of GV, glycoprotein NMB (GPNMB) expression, and survival in patients with metastatic uveal melanoma. Eligible patients with metastatic uveal melanoma who had not previously been treated with chemotherapy received GV 1.9 mg/kg every three weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included GPNMB expression, progression-free survival (PFS), overall survival (OS), and toxicity analysis. GPNMB expression was assessed pre- and post-treatment via immunohistochemistry for patients with available tumor tissue. Out of 35 patients who received treatment, two patients had confirmed partial responses (PRs; 6%), and 18 patients had a stable disease (SD; 51%) as the best objective response. 38% of the patients had stable disease >100 days. The grade 3 or 4 toxicities that occurred in two or more patients were neutropenia, rash, hyponatremia, and vomiting. The median progression-free survival was 3.1 months (95% CI: 1.5–5.6), and the median overall survival was 11.9 months (95% CI 9.0–16.9) in the evaluable study population. GV is well-tolerated in metastatic uveal melanoma. The disease control rate was 57% despite a low objective response rate. Exploratory immune correlation studies are underway to provide insight into target saturation, combination strategies, and antigen release.