Immune dysregulation is a hallmark of clinically active multiple myeloma (MM). Interactions between malignant clonal cells and immune cells within the bone marrow microenvironment are associated with the formation of a milieu favorable to tumor progression. IL-10, TGF-β and other immunoregulatory pathways are upregulated, promoting angiogenesis, tumor cell survival and inhibition of the native immune response. Transcriptomic evaluation of the bone marrow microenvironment reveals polarization of the T cell repertoire towards exhaustion and predominance of accessory cells with immunosuppressive qualities. These changes facilitate the immune escape of tumor cells and functional deficiencies that manifest as an increased risk of infection and a reduction in response to vaccinations. Immunotherapy with Chimeric Antigen Receptor (CAR) T cells and other cellular-based approaches have transformed outcomes for patients with advanced MM. Characterization of the immune milieu and identification of biomarkers predictive of treatment response are essential to increasing durability and allowing for the incorporation of novel strategies such as cancer vaccines. This paper will review the current use of cancer vaccines and CAR T cell therapy in MM as well as potential opportunities to expand and improve the application of these platforms.
Patients with urothelial carcinoma (UC) tend to be older and frailer with a large number of chronic medical conditions. This is particularly pronounced in those with locally advanced or metastatic UC. Prior to 2016, treatment options in advanced urothelial carcinoma (aUC) were limited to chemotherapy, and as a result, a large number of patients were not receiving diseasedirected therapy. Over the last six years, multiple alternative modalities including immune checkpoint inhibitors, enfortumab vedotin, sacituzumab govitecan and erdafitinib have been introduced. They are being used clinically in older and frail patients, but their efficacy and safety profiles remain underexplored in these populations. Based upon available evidence, age does not appear to impact the efficacy and tolerance of immune checkpoint inhibitors if patients are fit enough to receive therapy. There is still not enough evidence to draw specific conclusions regarding the use of enfortumab vedotin, sacituzumab govitecan and erdafitinib in older and frail patients. Regardless, in all older patients with aUC, it is critical to evaluate for frailty through geriatric screening tools and comprehensive assessments. Combining these evaluations with consideration of an individual patient's goals should be the foundation upon which therapeutic decisions are made in this population of patients. Key Points Age is not an independent predictor of safety or efficacy in the management of aUC, but instead, should serve as a signal to providers to assess for frailty, which can have a significant impact on outcomes. In older and frailer patients with advanced urothelial carcinoma, immune checkpoint inhibitors appear to be a well-tolerated treatment modality in the first and second line settings. At present, there is not enough data to comment definitively on the efficacy and safety of enfortumab vedotin, sacituzumab govitecan and erdafitinib in older and frail patients.2 Setting the Stage: The Introduction of ICIs, Enfortumab Vedotin, Sacituzumab Govitecan and Erdafitinib Since the 1980's, cisplatin has been the primary agent in aUC. It is the foundation upon which multiple combination regimens have been developed including methotrexate, vinblastine, adriamycin and cisplatin (MVAC) as well as gemcitabine plus cisplatin (GC) [13]. Ultimately, a head-to-head phase III trial of GC versus MVAC demonstrated similar overall response rate, progression free survival (PFS) and overall survival (OS), but given less adverse effects associated with GC, it has been the preferred first-line (1L) regimen in cisplatin-eligible patients [14][15]. Prior to 2016, the preferred therapy in cisplatin-ineligible patients was carboplatin and gemcitabine. Carboplatin-based regimens are inferior to cisplatin-based regimens with worse objective and complete responses, but they are better tolerated in frailer patients [16][17]. In those deemed platinum-ineligible, non-platinum-based regimens centered on the use of gemcitabine, but even still, as much as 23.8% -48.4% of patients were n...
338 Background: OP-35 is a publicly reported quality metric aimed at reducing preventable emergency department (ED) visits and hospitalizations in patients with cancer on chemotherapy. During the COVID-19 surge, one academic medical center opened the Respiratory Emergent Evaluation Service (REES) Unit, an urgent care clinic for patients with cancer and symptoms of COVID-19. In addition to preventing potential COVID-19 exposures in the clinic, this oncology-staffed urgent care evaluated patients who may have otherwise presented to the ED. We investigated the association between the REES urgent care clinic and patient ED evaluations for OP-35 diagnoses. Methods: This single center retrospective analysis included patients with cancer receiving infusion and oral chemotherapy who presented to the ED within 30 days of treatment. ED visits occurred between 1/2019-12/2021, including when the REES unit was open (3/2020-6/2021). Preventable ED visits were defined as having one of ten primary diagnoses, which have been identified by OP-35. Of these, COVID-related diagnoses included fever, pneumonia, sepsis, neutropenia and diarrhea. Interrupted time series analyses were utilized to investigate the association between the REES unit opening and preventable ED visits. Results: 3,107 patients on chemotherapy were assessed in the ED from 1/2019-12/2021. Per week, there were 19.9 ED visits, 39.7% of which were for OP-35 diagnoses. When the REES unit opened, there was a 30% (95% CI -53% to -7%) reduction in preventable ED visits, corresponding to 2.62 (95% CI -4.61 to -0.63) fewer preventable ED evaluations per week. The primary driver of this reduction were presentations for COVID-related diagnoses, as there were 38% (95% CI -76% to -0.3%) fewer preventable ED visits weekly. During this period, there were approximately 6.9 patient visits per week to the REES unit. Conclusions: The introduction of an oncology urgent care clinic focusing on patients with symptoms of COVID-19 was associated with a reduction in potentially preventable ED visits. This analysis demonstrates the potential value of oncology urgent care clinics in reducing ED overcrowding and decreasing OP-35 related evaluations, which has patient experience, infection exposure and financial implications.[Table: see text]
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