Citations

5000 Background: It is clinically challenging to integrate genomic classifier results that report a continuous numerical risk of recurrence into treatment decisions for prostate cancer (PCa). We aimed to develop a novel clinical-genomic risk system that can readily be incorporated into treatment guidelines for localized PCa. Methods: Four multi-center cohorts (n = 6928 men; 5937 prospective samples and 991 retrospective samples with long-term follow-up) were utilized to identify and validate our clinical-genomic risk system in radical prostatectomy (RP) samples and subsequently in pre-treatment biopsy samples. All patients’ FFPE tissue underwent microarray analysis, and the expression values for 22 prespecified biomarkers that constitute Decipher were extracted. Cumulative incidence curves were constructed to estimate metastasis risk. C-indices were calculated to compare NCCN and CAPRA score to our clinical-genomic system. Results: With a median follow-up of 8 years for men in our RP cohort, the 10-year distant metastasis rates for NCCN low, favorable-intermediate, unfavorable-intermediate, and high-risk were 7.8%, 9.4%, 40.1%, and 41.4%, respectively. Our 3-tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.7%, 30.7%, and 57.7%, for low, intermediate, and high-risk, which were validated in our pre-treatment biopsy cohort with 10-year rate of distant metastasis of 0%, 30.3%, and 63.2%, respectively. C-indices for the clinical-genomic system (0.84, 95%CI 0.62-0.92) were significantly improved over NCCN (0.71, 95%CI 0.59-0.84) and CAPRA (0.71, 95%CI 0.60-0.81) score. A total of 33.4% of men would be reclassified by the clinical-genomic system, and specifically 17.1%, 41.3%, and 19.4% of men in NCCN low, intermediate and high risk groups would be reclassified by our new system. Conclusions: The use of a readily available genomic classifier in combination with clinicopathologic variables can generate a simple to use 3-tier clinical-genomic risk system that is highly prognostic for distant metastasis, is more accurate than clinical risk, and can be easily incorporated into NCCN guidelines to inform treatment decisions.

3010 Background: To test the safety and efficacy of the CAR T cell modality in relapsed/refractory multiple myeloma (MM), we have designed a second-generation CAR construct targeting B cell maturation antigen (BCMA) to redirect T cells to MM. bb2121 consists of autologous T cells transduced with a lentiviral vector encoding a novel CAR incorporating an anti-BCMA scFv, a 4-1BB costimulatory motif and a CD3-zeta T cell activation domain. We will report updated safety and efficacy following initial results (Berdeja et al, ENA 2016). Methods: CRB-401 (NCT02658929) is a multi-center phase 1 dose escalation trial of bb2121 in patients with relapsed and/or refractory MM who have received ≥ 3 prior regimens, including a proteasome inhibitor and an immunomodulatory agent, or are double-refractory, and have ≥ 50% BCMA expression on plasma cells. Peripheral blood mononuclear cells are collected via leukapheresis. Patients undergo lymphodepletion with Flu (30 mg/m 2 ) / Cy (300 mg/m 2 ) daily for 3 days then receive 1 infusion of bb2121. The study follows a standard 3+3 design with planned dose levels of 5, 15, 45, 80 and 120 x 10 7 CAR+ T cells. Results: As of November 18, 2016, 11 patients had been infused with bb2121 in the first 4 dose cohorts, and 9 patients had reached at least 1 month of follow-up. As of data cut-off, no dose-limiting toxicities and no > Grade 2 neurotoxicities or cytokine release syndrome (CRS) had been observed. Grade 1-2 CRS had been reported in 8/11 (73%) treated patients. All patients treated with doses of 15.0 x 10 7 or higher remained on study and the overall response rate (ORR) in the 6 evaluable patients at these doses was 100%, including 2 sCRs and 2 MRD-negative responses (1 sC, 1 VGPR). CAR+ T cell expansion has been demonstrated consistently. An additional 6 months of follow up on previously reported results and initial data from an additional ~10 patients will be presented. Conclusions: bb2121 shows promising efficacy at dose levels above 5 x 10 7 CAR+ T cells, including 2 sCRs and ongoing clinical responses at 6 months, with mild and manageable CRS to date. These initial data support the potential of CAR T therapy with bb2121 as a new treatment paradigm in MM. Study sponsored by bluebird bio. Clinical trial information: NCT02658929.

BACKGROUND: Excessive perioperative fluid administration likely increases postoperative cardiovascular, infectious, and GI complications. Early administration of diuretics after elective surgery facilitates rapid mobilization of excess fluid, potentially leading to decreased bowel edema, more rapid return of bowel function, and reduced length of hospital stay. OBJECTIVE: This study aimed to evaluate the benefit of early diuresis after elective colon and rectal surgery in the setting of an enhanced recovery after surgery practice. DESIGN: This was a prospective study. SETTINGS: The study was conducted at a quaternary referral center. PATIENTS: A randomized, open-label, parallel-group trial was conducted in patients undergoing elective colon and rectal surgery at a single quaternary referral center. INTERVENTION: The primary intervention was administration of intravenous furosemide plus enhanced recovery after surgery on postoperative day 1 and 2 versus enhanced recovery after surgery alone. MAIN OUTCOME MEASURES: The primary outcome was length of hospital stay. Secondary outcomes included 30-day readmission rate, time to stool output during hospitalization after surgery, and incidence of various complications within the first 48 hours of hospital stay. RESULTS: In total, 123 patients were randomly assigned to receive either furosemide plus enhanced recovery after surgery (n = 62) or enhanced recovery after surgery alone (n = 61). Groups were evenly matched at baseline. At interim analysis, length of hospital stay was not superior in the intervention group (80.6 vs 99.6 hours, p = 0.564). No significant difference was identified in the rates of nasogastric tube replacement (1.6% vs 9.7%, p = 0.125). Time to return of bowel function was significantly longer in the intervention group (45.4 vs 48.8 hours, p = 0.048). The decision was made to end the study early because the conditional power of the study favored futility. LIMITATIONS: This was a single-center study. CONCLUSIONS: Early administration of furosemide does not significantly reduce the length of hospital stay after elective colon and rectal surgery in the setting of enhanced recovery after surgery practice. See Video Abstract at http://links.lww.com/DCR/A714.

Background There is currently a lack of consensus on how health-related quality of life and other patient-reported outcome measures in cancer randomized clinical trials are analyzed and interpreted. This makes it difficult to compare results across randomized controlled trials (RCTs) synthesize scientific research, and use that evidence to inform product labeling, clinical guidelines, and health policy. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data for Cancer Clinical Trials (SISAQOL) Consortium aims to develop guidelines and recommendations to standardize analyses of patient-reported outcome data in cancer RCTs. Methods and Results Members from the SISAQOL Consortium met in January 2017 to discuss relevant issues. Data from systematic reviews of the current state of published research in patient-reported outcomes in cancer RCTs indicated a lack of clear reporting of research hypothesis and analytic strategies, and inconsistency in definitions of terms, including “missing data,”“health-related quality of life,” and “patient-reported outcome.” Based on the meeting proceedings, the Consortium will focus on three key priorities in the coming year: developing a taxonomy of research objectives, identifying appropriate statistical methods to analyze patient-reported outcome data, and determining best practices to evaluate and deal with missing data. Conclusion The quality of the Consortium guidelines and recommendations are informed and enhanced by the broad Consortium membership which includes regulators, patients, clinicians, and academics.

AbstractBackground: We studied the utility of the tumor suppressor Tristetraprolin (TTP, ZFP36) as a clinically relevant biomarker of aggressive disease in prostate cancer patients after radical prostatectomy (RP).Methods: TTP RNA expression was measured in an RP cohort of patients treated at Moffitt Cancer Center (MCC) and obtained from six publically available RP datasets with biochemical recurrence (BCR; total n = 1,394) and/or metastatic outcome data (total n = 1,222). TTP protein expression was measured by immunohistochemistry in a tissue microarray of 153 MCC RP samples. The time to BCR or metastasis based on TTP RNA or protein levels was calculated using the Kaplan–Meier analysis. Univariable and multivariable Cox proportional hazard models were performed on multiple cohorts to evaluate if TTP is a clinically relevant biomarker and to assess if TTP improves upon the Cancer of the Prostate Risk Assessment postsurgical (CAPRA-S) score for predicting clinical outcomes.Results: In all of the RP patient cohorts, prostate cancer with low TTP RNA or protein levels had decreased time to BCR or metastasis versus TTP-high tumors. Further, the decreased time to BCR in TTP-low prostate cancer was more pronounced in low-grade tumors. Finally, pooled survival analysis suggests that TTP RNA expression provides independent information beyond CAPRA-S to predict BCR.Conclusions: TTP is a promising prostate cancer biomarker for predicting which RP patients will have poor outcomes, especially for low-grade prostate cancer patients.Impact: This study suggests that TTP RNA expression can be used to enhance the accuracy of CAPRA-S to predict outcomes in patients treated with RP. Cancer Epidemiol Biomarkers Prev; 27(11); 1376–83. ©2018 AACR.