Renal tubule epithelia represent the primary site of damage in acute kidney injury (AKI), a process initiated and propagated by the infiltration of macrophages. Here we investigated the role of resident renal macrophages and dendritic cells in recovery from AKI after ischemia/reperfusion (I/R) injury or a novel diphtheria toxin-induced (DT-induced) model of selective proximal tubule injury in mice. DT-induced AKI was characterized by marked renal proximal tubular cell apoptosis. In both models, macrophage/dendritic cell depletion during the recovery phase increased functional and histologic injury and delayed regeneration. After I/R-induced AKI, there was an early increase in renal macrophages derived from circulating inflammatory (M1) monocytes, followed by accumulation of renal macrophages/dendritic cells with a wound-healing (M2) phenotype. In contrast, DT-induced AKI only generated an increase in M2 cells. In both models, increases in M2 cells resulted largely from in situ proliferation in the kidney. Genetic or pharmacologic inhibition of macrophage colony-stimulating factor (CSF-1) signaling blocked macrophage/dendritic cell proliferation, decreased M2 polarization, and inhibited recovery. These findings demonstrated that CSF-1-mediated expansion and polarization of resident renal macrophages/dendritic cells is an important mechanism mediating renal tubule epithelial regeneration after AKI.

11017 Background: Most GISTs are driven by mutations in KIT and PDGFRa and secondary mutations are felt to confer resistance to TKIs. In advanced/metastatic GIST, the benefit of second line TKIs and beyond is progressively less after imatinib failure. As such, novel non-TKI approaches are important to explore. Here we report interim analyses of safety and efficacy in advanced GIST patients treated with immunotherapy. Methods: Patients with advanced/metastatic GIST refractory to at least imatinib were enrolled on a randomized, parallel group, unblinded Phase 2 trial of either nivo (240 mg Q2wks) or nivo (240 mg Q2wks) with ipi (1mg/kg Q6wks) for up to 2 years. The primary endpoint was the objective response rate(ORR) of nivo alone or nivo + ipi by RECIST 1.1 criteria. Imaging was assessed by investigator and 3 independent radiologists. Patients were randomized 1:1 and were restaged every 8 weeks. With a sample size of 20 per group, an exact binomial test with a nominal 0.050 one-sided significance level will have 82% power to detect the difference between the null hypothesis response rate 1.5% and the alternative response rate of 15%. Secondary objectives are to ascertain the PFS, CBR, RR by Choi criteria and safety. Blood and biopsies are also being collected. Results: At cutoff, 29 patients (27 evaluable) with a median of 3 (1-7) lines of prior therapies have started on trial. In the nivo only arm, 7/15 pts had a best response of SD for a CBR of 46.7% with the median PFS being 8.57 wks. In the nivo + ipi arm, 1/12 patients had a PR and 2/12 have SD for a CBR of 25.0% (95% exact C.I. 5.5%-57.2%) with a median PFS of 9.1 wks. 8 patients have been on therapy for more than 6 months and two patients with a KIT Exon 17 mutation had radiographic disease shrinkage. Most AEs were grades 1-2 with fatigue (37%) being the most common. 4 Grade 3/4 AEs occurred in the nivo and ipi arm (hyperglycemia, weakness, diarrhea x 2) and 4 grade 3/4AEs occurred in the nivo arm (DKA, hyperglycemia, rash, fatigue). Pretreatment biopsies have been obtained in all patients and blood has been collected on all patients for correlative analysis. Conclusions: In a heavily pretreated GIST population, responses and disease control with both nivo and nivo + ipi were observed. To date, the drugs have been well tolerated and no new safety signals have been observed in this disease state. Clinical trial information: NCT02880020.

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2062 Background: Advances in health technology provide potential tools that can aid in assessing and monitoring the functional status of the growing older adult population diagnosed with cancer. We piloted a novel wearable monitoring platform, Sensing in At-Risk Populations (SARP), which consists of a smartwatch, software application for health monitoring, and a central data processing and analytics engine. Methods: This is a prospective single center, single arm study, utilizing the SARP platform to risk stratify older adults with cancer and determine correlation with treatment-related adverse events and healthcare utilization. Pts age ≥60 undergoing active treatment, were offered participation. Pts were instructed to wear the smartwatch for ≥7 days. We used Kruskal-Wallis to correlate wearable data with clinical outcomes: toxicity, ED visits, hospitalizations, and mortality. We also compared SARP data to independently collected ECOG PS, CARG score, ADLs, and IADLs. Results: From 8/2016 to 8/2017, 54 older adults were consented, and 26 had wearable data available for analysis. The average age was 72 years, with 18 males and 8 females. 12 pts had ECOG PS of 0, 12 with ECOG of 1, and 2 with ECOG of 2. 4 pts had CARG score of low, 17 intermediate, and 3 high. Energy intensity was significantly correlated with ED visits, with an effect size of 0.95 (p = 0.04). Similarly, energy intensity and hospitalizations had an effect size of 0.87 (p = 0.06). The CARG scores were noted to be significantly correlated with dose delay and dose reduction with an effect size 0.45 (p = 0.05) and 0.4 (p = 0.05), respectively. Spearman correlation analysis demonstrated that walking time, active time, and energy intensity positively correlate with ADLs and IADLs, and inversely correlated with ECOG PS and CARG risk. Conclusions: Though this is a limited study due to sample size, the overall trend demonstrated that the SARP platform offers an adjunct tool in assessing and risk stratifying older patients with cancer undergoing active therapy. Additional cohorts are now enrolled with an at-home monitoring system. [Table: see text]