Cyclophosphamide addition to pomalidomide/dexamethasone is not necessarily associated with universal benefits in RRMM.

In the backdrop of rapidly changing relapsed/refractory (RR) multiple myeloma (MM) treatment schema that mainly evolves around immunotherapies, it is easy to disregard more traditional drugs. Finding the best partner for pomalidomide, a potent third-generation immunomodulatory drug, is an important agenda we face as a community and cyclophosphamide addition has been used for outcomes augmentation. We carried out this real-world study to identify patients who will show durable response to pomalidomide and those who will benefit from cyclophosphamide addition. A total of 103 patients (57 in pomalidomide-dexamethasone [Pd] group versus 46 in pomalidomide-cyclophosphamide-dexamethasone [PCd]) were studied. They were previously treated with bortezomib (98.1%) or lenalidomide (100%) and previous lines of therapy were median 3 lines. Significantly better overall response rate (ORR) was seen in the PCd (75.6%) than Pd (41.7%) group (p = 0.001), but no differences in survival outcomes. Subgroup analysis revealed that high-risk myeloma features, poor response to lenalidomide or bortezomib had superior ORRs when cyclophosphamide was added. Also, long-term responders for pomalidomide were associated with excellent response to previous IMiD treatments. Pomalidomide-based therapy was discontinued in five patients due to intolerance or adverse events, but there was no mortality during treatment. In conclusion, we showed that pomalidomide-based treatment is still relevant and can ensure durable response in RRMM setting, especially for patients who responded well to previous lenalidomide. Addition of cyclophosphamide to Pd is associated with better ORR, and can be positively considered in fit patients with high-risk MM, extramedullary disease, and less-than-satisfactory response to previous lenalidomide treatment.

A Descriptive Study of Emergency Department Visits Within 30 Days of Discharge.

BACKGROUND: Unnecessary emergency department (ED) visits are a crucial consideration in discharge planning for acutely admitted patients. This study aimed to identify the reasons for unnecessary visits to the ED within 30 days of discharge from a medical hospitalist unit. METHODS: We performed a retrospective review of patients discharged in 2018 from a medical unit of tertiary teaching hospital in Korea. The authors discussed in-depth and determined whether or not an ED visit was unnecessary, and further classified the causes of unnecessary visits into three categories. RESULTS: The mean age of the patients was 62.9 years (range, 15-99 years), and among the 1,343 patients discharged from the unit, 720 (53.6%) were men. Overall, 215 patients (16.0%) visited the ED within 30 days after discharge; among them, 16.3% were readmitted. Of the 215 cases of ED visits within 30 days after discharge, 57 (26.5%) were considered unnecessary. Of these, 30 (52.6%) were categorized as having failed care transition, 15 (26.3%) had unestablished care plans for predictable issues, and 12 (21.1%) had insufficient patient education. CONCLUSION: A substantial number of short-term ED visits by discharged multimorbid or older medical patients were considered unnecessary. Discharging patients with a thorough discharge plan is essential to avoid unnecessary ED visits.

Clinical Frailty Scale, K-FRAIL questionnaire, and clinical outcomes in an acute hospitalist unit in Korea.

BACKGROUND/AIMS: Frailty increases the risks of in-hospital adverse events such as delirium, falls, and functional decline in older adults. We assessed the feasibility and clinical relevance of frailty status in Korean older inpatients using the Clinical Frailty Scale (CFS) and Korean version of the Fatigue, Resistance, Ambulation, Illnesses, & Loss of Weight scale (K-FRAIL) questionnaires. METHODS: Frailty status was measured using the Korean-translated version of the CFS and K-FRAIL questionnaire within 3 days from admission in 144 consecutive patients aged 60 years or older. The correlation between CFS and K-FRAIL score was assessed. The criterion validity of CFS was assessed using receiver operating characteristic analysis. As outcomes, delirium, bedsore, length of stay (LOS), in-hospital mortality, and unplanned 30-day readmission were measured by reviewing medical records. RESULTS: The mean age of the study population was 70.1 years (range, 60 to 91), and 75 (52.1%) were men. By linear regression analysis, CFS and K-FRAIL were positively correlated (B = 0.72, p < 0.001). A CFS cutoff of ≥ 5 maximized sensitivity + specificity to classify frailty using K-FRAIL as a reference (C-index = 0.893). Higher frailty burden by both CFS and K-FRAIL was associated with higher LOS and bedsores. Unplanned readmission and in-hospital mortality were associated with higher CFS score but not with K-FRAIL score, after adjusting for age, gender, polypharmacy, and multimorbidity. CONCLUSION: Frailty status by CFS was associated with LOS, bedsores, unplanned readmission, and in-hospital mortality. CFS can be used to screen high-risk patients who may benefit from geriatric interventions and discharge planning in acutely hospitalized older adults.

Programmed death-ligand 1 expression level as a predictor of EGFR tyrosine kinase inhibitor efficacy in lung adenocarcinoma.

BACKGROUND: The main objective of this study was to investigate the impact of programmed death-ligand 1 (PD-L1) expression on the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in patients with advanced non-small cell lung cancer (NSCLC). METHODS: This study analyzed 108 patients with NSCLC who had received EGFR-TKI as first-line systemic treatment at Seoul National University Bundang Hospital and Seoul National University Hospital between December 2012 and October 2018. The National Cancer Center Research Institute (NCCRI) and The Cancer Genome Atlas (TCGA) datasets were analyzed to investigate the mechanisms underlying EGFR-TKI-resistance in tumors with high PD-L1 expression. RESULTS: Among the 108 patients, 55, 37, and 16 had negative (PD-L1 Tumor proportion score <1%), weak (1-49%), and strong (≥50%) PD-L1 expression, respectively. Patients with strong PD-L1 expression had significantly shorter median progression-free survival (PFS; 7.07 months) than patients with weak (14.73 months, P<0.001) or negative (12.70 months, P=0.001) PD-L1 expression. After adjustment for covariates by Cox regression, PD-L1 expression remained a significant indicator of adverse prognosis. In EGFR-TKI-refractory patients, the frequency of T790M mutation and the PFS following treatment with third-generation EGFR-TKI and PD-1 antibody were similar in the three groups. TCGA and NCCRI database analysis showed that high PD-L1 expression in EGFR-mutated NSCLCs correlated with IL-6/JAK/STAT3 signaling and high MUC16 mutation frequency. CONCLUSIONS: Strong PD-L1 expression in tumors might be a surrogate indicator of poor response to first-line EGFR-TKIs in NSCLC patients with sensitizing EGFR mutations, and may reflect a de novo resistance mechanism involving JAK-STAT signaling.