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7505 Background: Novel agents (NA) targeting B cell receptor kinases and Bcl-2 have substantially improved outcomes in CLL; however, the development of RS in CLL patients (pts) on NAs has been observed, and has not been systematically evaluated. Methods: We retrospectively reviewed pts at 9 academic centers diagnosed with pathologically-confirmed RS from 2011-16. Informed consent was provided through IRB-approved protocols. Descriptive statistics were utilized and overall survival (OS) was calculated from RS diagnosis (dx) to death or last follow-up by Kaplan-Meier. Results: 71 pts who developed RS on NAs for CLL were identified. Median age at CLL dx was 55 yrs (range 21-82), median of 3 therapies (range 0-12) prior to the NA. 68% pts were fludarabine-refractory, and 5 pts (7%) had relapsed post alloHCT. Median time from CLL dx to initiation of NA was 68.5 mo. (range 1.1-246.2). FISH at NA initiation: del(17p) 30/61 (49%), del(11q) 15/61 (25%), trisomy 12 15/61 (25%). Complex karyotype was present in 40/53 (75%). 46/52 (88%) were IGHV unmutated, VH1-69 10/43 (23%), VH4-39 4/43 (9%). 59 (83%) pts were on a BTK inhibitor, 6 (8%) PI3K inhibitor, 6 (8%) venetoclax. RS histology: DLBCL (87%), plasmablastic (6%), Hodgkin (4%), 3% other. RS Ki-67%: >90 (23%), 75-90 (25%), 50-75% (25%), <50% (28%). Median time from start of NA to RS dx was 9.1 mo (range 0.9-48.2), with 65% developing RS within 12 mo. of starting NA. In 56 pts, 19 different regimens were used as initial RS therapy, including: R-EPOCH (36%), R-CHOP (20%), checkpoint blockade (9%), OFAR (7%), or a different NA (7%). Of the 48 pts evaluable for response, ORR was 42% (15% CR, 27% PR). In 29 evaluable pts receiving R-EPOCH/CHOP, ORR was 48% (21% CR). With a median follow-up of 10.6 mo., median OS was only 3.3 mo. (95%CI 2.2-6.0), though none of the 7 pts who achieved CR has died. Conclusions: We report to our knowledge the largest series of CLL pts developing RS on NAs. Pts often had high risk CLL, particularly complex cytogenetics, and RS frequently developed within the first year of NA therapy. Substantial variation exists in treatment, and outcomes are poor for those who do not achieve CR. Identification of molecular drivers of RS and development of novel treatment strategies are urgently needed.

e18514 Background: Standard induction therapy for acute myeloid leukemia (AML) includes “cytarabine and anthracycline”. Anthracyclines are known to cause acute, subacute and chronic cardiac complications ( Lefrak , EA et al, Cancer 1973:32(2):302-314; Singal, PK et al, NEJM 1998;339(13):900-905). It is recommended to do base line cardiac function assessment with echocardiogram prior to induction therapy containing anthracycline. This study was done to find the frequency of changes made in avoiding anthracycline usage following this evaluation. Methods: The Mayo clinic data base was interrogated to identify patients with newly diagnosed AML who underwent echocardiogram prior to anthracycline containing induction chemotherapy. Echocardiogram results, including left ventricular ejection fraction (LVEF), diastolic dysfunction, valvular disease, and any resultant treatment alterations were reviewed. Results: Three hundred twenty six patients were identified. The median (range) age was 61 (17-82) years and 62% were male. The median (range) LVEF was 65% (30-87), and 3 (0.9%) patients had LVEF < 50% (range 30-47%). Of these 3 patients, 1 had 4 vessel CABG a decade ago, his EF was 46% and treated with full dose idarubicin; 2 of them presented with blastic crisis, 1 had EF 46% and improved to 51% after 5 days and then given daunorubicin, the other one had an EF of 30% and treated with 50% dose reduced cytarabine alone. Sixty five (23%) patients had previous chemotherapy or radiation exposure, including 24 (7.4 %) with previous anthracycline, 14 (4.3%) had prior radiation to the chest wall. No patient with previous chemotherapy or radiation exposure had a reduced LVEF. Conclusions: Echocardiography prior to anthracycline therapy rarely detects abnormal LVEF. Screening echo may be helpful in those presented with leukemic blastic crisis or had previous exposure to chemo-radiation.

e18154 Background: Due to an increase in the elective decision to pursue contralateral prophylactic mastectomy (CPM), the incidence of bilateral mastectomy (BM) with/without postmastectomy reconstruction (R) [BM+/-R] has increased in the last decade. While prior studies at academic centers have investigated concerns regarding its impact on subsequent cancer therapy, we hypothesized that BM+/-R is associated with a delay in initiation of adjuvant therapy (AT) in a community oncology clinic. Methods: This study involved chart review of all patients who underwent mastectomy as definitive surgery for stage I-III breast cancer between 2007 and 2012 and were subsequently followed at Essentia Health Cancer Center. The primary endpoint of the study was the proportion of patients receiving subsequent AT within 6 weeks of surgery (TST6) when compared between different surgical groups. Results: A total of 478 patients were included in the study, with a median age of 63 years. Patients were divided into 4 groups, BM-R (n = 133), BM+R (n = 73), unilateral mastectomy (UM) –R (n = 244) and UM+R (n = 28). Significant demographic differences were identified between the groups including age ( p< 0.001), medical comorbidities ( p< 0.001), and BMI ( p< 0.001). The incidence of any major post-operative complication (including flap/implant failure, infection and wound necrosis/dehiscence) or additional surgeries within 6 weeks of surgery was higher in patients undergoing reconstruction, [BM+R (19%) and UM+R (18%)] compared to those who did not [BM-R (6%) and UM-R (4%)] ( p< 0.001). Patients having major complications or needing additional surgeries within 6 weeks had a lower adjusted likelihood of achieving TST6 compared to those who did not (OR = 0.35; p= 0.009). However, there was no significant difference in TST6 between the surgical groups ( p= 0.31). Conclusions: Immediate post-mastectomy reconstruction is associated with a significantly increased risk of postoperative complications or need for additional surgeries within 6 weeks. In an appropriately selected patient population, CPM and reconstruction do not significantly delay subsequent AT in a community oncology clinic.

9517 Background: Although PD-1/L1 axis directed therapies induce durable responses in some mm patients (pts), biomarkers of response remain elusive. We hypothesized that quantifying key immune suppression mechanisms within the tumor microenvironment would provide superior predictors of response to anti-PD-1 compared with single marker assessment. Methods: Pre-treatment tumor biopsies from 124 mm pts treated with anti-PD-1 at 7 academic centers were fluorescently stained with multiple immune markers in discovery (n = 24) and validation (n = 100) cohorts. Selected biomarker signatures, PD-1/PD-L1 interaction score (proportion of PD-1+ cells co-localized with PD-L1) and IDO1/HLA-DR co-expression were evaluated for anti-PD-1 treatment response and survival. Slides were imaged using Vectra; biomarker positive cells and their co-localization were objectively quantified in pathologist-selected regions using novel Automated Quantitative Analysis (AQUA) algorithms. Results: In the discovery cohort, high levels of PD-1/PD-L1 interaction score and/or IDO1/HLA-DR coexpression was strongly positively associated with response to anti-PD-1 (p = 0.0005). In contrast, other individual biomarkers (PD-1, PD-L1, CD8) were not associated with response or survival (p > 0.10). This finding was replicated in the validation cohort: pts with high PD-1/PD-L1 and/or IDO1/HLA-DR were more likely to respond to treatment (p = 0.009). These pts also experienced a three-fold increase in progression free survival (hazards ratio (HR) = 0.33; p = 0.003) and overall survival (HR = 0.34; p = 0.004). Multivariate analyses revealed that these findings were independent of BRAF mutation, stage, LDH and prior therapy. In the combined cohort (n = 124), 80% of responding pts had higher levels of PD-1/PD-L1 interaction scores and/or IDO1/HLA-DR. In contrast, PD-L1 expression alone (≥1% or ≥50%) was not predictive of PFS or OS (p > 0.1). Conclusions: This novel multiplexed method profiling key tumor-immune suppression pathways identified mm pts likely to respond to anti-PD-1 therapy. This method could help stratify patients for PD-1 monotherapy and be useful in guiding future clinical trials.

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.

AbstractBackground/ObjectivesSpecific maternal risk factors have recently been identified in the development of infantile hemangiomas (IH), including gestational diabetes (GDM), maternal antihypertensive medication use or gestational hypertension (GHTN), maternal progesterone use, and artificial reproductive technologies (ART). We sought to explore the change in incidence of these risk factors over time and determine their association with the increased incidence of hemangiomas over 35 years, as previously reported.MethodsThe charts of 869 mother and infant pairs (infants previously diagnosed with IH between January 1, 1976, and December 31, 2010) were reviewed for prenatal complications. Rates of the prenatal complications over the 35‐year period in birth mothers of infants diagnosed with IH were determined and evaluated by year of diagnosis (1976‐1990, 1991‐2000, and 2001‐2010).ResultsOver the 35‐year period in which the incidence of IH was previously examined, maternal age at delivery, prepregnancy body mass index (BMI), use of ART, maternal progesterone use, placental abnormalities, and GDM also increased.ConclusionsGDM, ART, and maternal progesterone use increased over the past 35 years, mirroring the previously reported trend of increasing incidence of IH. Maternal age and BMI also increased in mothers of infants with IH. Further exploration of this association may direct future research in the pathogenesis of infantile hemangiomas.