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While localized penile cancers are typically treated surgically and metastatic penile cancers benefit from standard chemotherapy, there have been studies on the horizon demonstrating immunotherapy as a novel approach to metastatic penile cancers that have failed standard chemotherapy. We report a case series of two patients who improved on immunotherapy after progressing with standard chemotherapy regimens. The first case describes a 64-year-old male with a penile mass and significant lymphadenopathy who had surgical resection and adjuvant chemotherapy prior to continued disease progression. He was started on anti-EGFR treatment and improved initially, but he eventually had progression of disease. The second case describes a 79-year-old male with a penile mass who was treated with surgical resection and started on adjuvant chemoradiation, but he developed recurrence and nodal involvement. Therefore, second-line therapy of the PD-L1 inhibitor was started in this patient. There were no available clinical trials for penile cancer patients who progressed beyond the standard surgical therapy and chemotherapy.

The phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a well studied signaling pathway that regulates diverse cellular functions including proliferation, metabolism, and transcription. Aberrant activation of this pathway has been implicated in multiple cancers. Genomic studies have shown that activating mutations in oncogenes as well as inactivating mutations in tumor suppressor genes are present across a variety of malignancies, including urothelial carcinoma. In bladder cancer, up to 40% of tumors exhibit constitutive activation of the PI3K/AKT/mTOR pathway. Current treatments for non–muscle-invasive disease confer a 5-year cancer-specific survival rate as high as 90%. However, patients with muscle-invasive, recurrent, or metastatic disease have a poor prognosis. Although the introduction of immune checkpoint inhibitors is certainly changing the therapeutic landscape and is a great addition to the platinum-based therapy that was the standard of care for the past 3 decades, it is anticipated that a great number of patients would fail to respond or their disease would progress with either chemotherapy or immunotherapy. Therefore, the use of agents that target members of the PI3K/AKT/mTOR pathway represent an attractive, alternative therapeutic strategy for patients with advanced urothelial carcinoma. In this review we describe the pathway, with a focus on the rationale for targeting the PI3K/AKT/mTOR pathway in patients with advanced urothelial carcinoma and considers the challenges that we face from the current clinical trials. Novel agents such as PI3K inhibitors and microRNA inhibitors that target this pathway might lead to durable responses especially when used in combination with chemotherapy or immune checkpoint inhibitors, however, toxicity remains an obstacle. Finally, in this review we discuss the importance of developing biomarkers to help select appropriate patients and identify optimal treatment options.

135 Background: Black patients have a disproportionately high incidence and mortality from lung cancer. Despite the importance of clinical trials, there continue to be significant racial disparities in recruitment for pivotal registration studies. In 2016, the FDA recommended reporting racial enrollment with a minimum of 5 categories (White, Black, Asian, American Indian or Alaskan Native [AIAN] and Native Hawaiian or Pacific Islander [NHPI]). The International Committee of Medical Journal Editors also recommend reporting race and ethnicity. We evaluated race reporting and representation in registration trials for thoracic cancers. Methods: We reviewed the FDA website and identified all new drug licensing indications in thoracic malignancies (small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC) and mesothelioma) from 2006 to 2020. NSCLC was further classified as EGFR+, ALK+, other mutation and NOS (no driver mutation). Clinical trials cited on the licensing label for market authorization were recorded and the corresponding registration trial publication was identified. If race was unreported or underreported (defined as ≤3 groups) in the licensing study, then additional information was obtained from clinicaltrials.gov. We calculated the proportion of registration trials meeting FDA criteria and the proportion of each racial group in trials. Results: From 2006-2020, we identified 55 new licensing indications, involving 26 unique drugs; 5 approvals in SCLC, 49 approvals in NSCLC and 1 in mesothelioma. Prior to the FDA race reporting guidelines, 33% (6/18) of registration studies did not meet FDA requirements. This improved to 27% (10/37) after the guideline introduction. Overall 29,545 patients participated in thoracic registration trials; 66% White, 22% Asian, 2% Black

Introduction: The addition of gemtuzumab ozogamicin (GO) to 7+3 chemotherapy for newly diagnosed acute myeloid leukemia (AML) has been shown to significantly improve event-free survival (EFS) for cytogenetically favorable-risk AML, with marginal benefit for intermediate-risk AML, and no benefit for cytogenetically adverse-risk AML. Of note, with the exception of mutated FLT3-ITD, little is known about the impact of GO in ELN 2017-defined genotypically adverse-risk AML, and a recent randomized trial found no EFS benefit for 7+3+GO in patients (pts) with genotypically favorable-risk, NPM1-mutated AML. Since 2017, our institution incorporated GO into 7+3-based inductions for all "non-adverse" risk AML pts, as defined by wild-type FLT3 and no abnormalities on rapid FISH analysis for del(5q)/monosomy 5, del(7q)/monosomy 7, and del(20q). We report our experience treating all pts with "non-adverse" risk AML-as defined by this algorithm-with 7+3+GO. Methods: An institutional database was queried in order to identify all pts ≥18 years old who received 7+3-based chemotherapy for newly diagnosed AML between 2017 and 2020; pts who received the FDA-approved fractionated dose of GO were included in the analysis. Data collection included demographic variables, karyotype/FISH, targeted PCR analyses, and multigene NGS panels for AML-related mutations including, but not limited to, mutations in FLT3, NPM1, CEBPA, TP53, RUNX1, and ASXL1. Outcome data included response to induction, relapse, and death, as well as hematopoietic cell transplant (HCT) rates, conditioning regimens, and post-transplant complications. Results: Between January 2017 and July 2020, 96 pts received 7+3-based induction at our institution. Of these, 29 (30%) received 7+3 in combination with GO. Median age at diagnosis was 46 years (range 23-66), with 17 (59%) males. Sixteen (55%) pts had ELN favorable-risk AML (5 [31%] by cytogenetics and 11 [69%] by genotype), 6 (21%) pts had ELN intermediate-risk AML, and 7 (24%) pts had ELN adverse-risk AML (4 [57%] by cytogenetics and 3 [43%] by genotype). Median time from diagnosis to start of induction was 4 days (range 0-43). For cytogenetically adverse-risk pts, median time from diagnostic bone marrow biopsy to receipt of adverse karyotype results was 8 days (7-14). Median time from start of induction to receipt of multigene NGS results for all pts was 15 days (3-32). Overall, 22 (76%) pts achieved remission. All genotypically adverse-risk pts (1 with mutated TP53 and 2 with mutated RUNX1) were refractory to induction, while 3 of 4 (75%) cytogenetically adverse-risk pts (1 with t(6;9), 1 with monosomy 7, and 2 with 11q23 abnormalities) achieved remission. Eight of the 29 (28%) pts proceeded to HCT, including 4 adverse-risk pts. Of the adverse-risk pts, all received myeloablative conditioning prior to HCT and 3 (75%) developed veno-occlusive disease (VOD), with 2 (50%) requiring defibrotide therapy. In favorable/intermediate-risk pts, 4 (18%) proceeded to HCT (2 intermediate-risk pts in first remission and 2 favorable-risk pts in second remission). Of these, 2 (50%) received myeloablative conditioning and 1 (25%) developed VOD. At last follow-up, 23 of 29 pts (79%) remained alive, with a median overall survival not reached (range 1-29 months) and a median EFS of 20 months (9-31). The percentage of ELN favorable-, intermediate-, and adverse-risk pts who remained event-free at last follow-up was 75%, 33%, and 43%, respectively. Discussion: This single-center, retrospective cohort describes the outcomes of pts with "non-adverse" risk AML who received induction chemotherapy with 7+3+GO according to a pre-defined algorithm. Using this algorithm, 30% of all pts receiving 7+3-based inductions received GO. Of these, nearly 25% were ultimately found to have adverse-risk AML as defined by ELN 2017 criteria, largely driven by long turn-around times for karyotyping and NGS multigene panel results. No patient with genotypically adverse-risk AML by ELN criteria responded to induction chemotherapy, and 75% of cytogenetically adverse-risk pts who proceeded to HCT developed VOD. Routine use of 7+3+GO induction outside of the context of cytogenetically favorable-risk AML remains controversial, and further study is needed to define the role of GO, particularly for pts with ELN genotypically adverse-risk AML. Table Disclosures Gotlib: Blueprint Medicines Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Chair of the Response Adjudication Committee and Research Funding, Research Funding; Deciphera: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: co-chair of the Study Steering Committee and Research Funding. Liedtke:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; GSK: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Muffly:Adaptive: Research Funding; Amgen: Consultancy; Servier: Research Funding. Mannis:AbbVie, Agios, Bristol-Myers Squibb, Genentech: Consultancy; Glycomimetics, Forty Seven, Inc, Jazz Pharmaceuticals: Research Funding.

Introduction Older adults with AML are often ineligible for high intensity chemotherapy and potentially curative allogeneic hematopoietic cell transplantation (HCT) due to poor performance status at presentation, comorbidities, and/or adverse genetic features associated with refractory disease and chemoresistance. Recently, the lower intensity combination of a hypomethylating agent and venetoclax (HMA/Ven) was shown to achieve durable responses in patients with AML. Despite this combination having been studied primarily in older, transplant-ineligible adults, a small subset of patients on the Phase 1b trial were successfully bridged to HCT (Pratz et al, 2019). We conducted a multi-center analysis assessing patient characteristics and clinical outcomes of patients treated with HMA/Ven who subsequently proceeded to HCT. Methods We retrospectively identified 51 adults who received HMA/Ven in either the front-line or relapsed/refractory (R/R) setting and underwent subsequent HCT between 2017 - 2019 at Stanford University, the University of California, San Francisco, and the University of California, Los Angeles. Patients received either azacitidine or decitabine in combination with venetoclax. Patients were evaluated for efficacy endpoints including: best response prior to HCT (complete remission [CR], CR with incomplete hematologic recovery [CRi], morphologic leukemia-free state [MLFS]), measurable residual disease (MRD) prior to HCT by flow cytometry (sensitivity threshold ≤1x10-4), and post-HCT relapse and survival. Results The median age at HCT was 65.5 years (24 - 76). Fifty-three percent of patients had a KPS of ≤ 80, and 29% had an HCT-CI of ³ 3. Fifty-seven percent had adverse-risk disease by 2017 European Leukemia Net criteria. The majority (63%) received decitabine; 23 (45%) received HMA/Ven as front-line induction and 28 (55%) for R/R disease. Compared to patients with R/R disease, patients who received front-line HMA/Ven were more likely to be older (67 vs 54 years, p = 0.003) and have a KPS ≤ 80 (65% vs 47%, p = 0.03). Patients with R/R disease had a median of 2 (1 - 4) lines of therapy prior to receiving HMA/Ven and 2 patients had undergone prior HCT. The number of HMA/Ven cycles prior to HCT varied considerably, with a median of 3 (1 - 11). The majority (78%) of patients achieved a complete remission prior to HCT. Of the patients who received front-line HMA/Ven, 83% achieved CR, 13% CRi, and 4% MLFS; 17 (74%) patients had a pre-HCT MRD assessment, of which 71% were MRD-negative. Of the patients who received HMA/Ven for R/R disease, 41% achieved CR, 22% CRi, 33% MLFS, and 4% had refractory disease; 24 (86%) of patients had a pre-HCT MRD assessment, of which 54% were MRD-negative. Across the full cohort, 49% of patients received non-myeloablative, 35% myeloablative, and 16% reduced intensity conditioning. The majority (94%) of patients received peripheral blood stem cell grafts; donor sources were 35% HLA-matched related, 43% HLA-matched unrelated, and 22% haploidentical. Following HCT, 100-day non-relapse mortality was 4%, 6-month overall survival (OS) was 85% and 6-month relapse-free survival (RFS) was 63%. Among patients who received front-line HMA/Ven, 6-month OS was 88% and 6-month RFS was 80%; among patients with R/R disease, 6-month OS was 81% and 6-month RFS was 51%. Patients who were MRD-negative had a 6-month OS of 87% and RFS of 75%; MRD-positive patients had 6-month OS of 73% and RFS of 46%. Among the 27 patients transplanted prior to July 1, 2019, 1-year OS and RFS were 78% and 59% for the entire cohort, 90% and 80% for the 10 patients receiving frontline HMA/Ven, and 71% and 47% for the 17 patients with R/R disease. Conclusion In patients with AML, an HMA in combination with venetoclax can achieve complete remissions-MRD-negative in many cases-thus providing a viable pathway to potentially curative HCT. This treatment pathway is especially important in older/unfit patients receiving front-line HMA/Ven due to ineligibility for high intensity induction chemotherapy, as well as those with relapsed/refractory and previously chemoresistant disease. Following HCT, patients treated in both settings had low NRM and favorable rates of disease response. Prospective studies are warranted to further explore the optimal use of HMA/Ven therapy as a bridge to successful transplant outcomes. Disclosures Muffly: Amgen: Consultancy; Adaptive: Research Funding; Servier: Research Funding. Logan:Abbvie: Consultancy; Amgen: Consultancy; Novartis: Consultancy; Amphivena: Research Funding; Autolus: Research Funding; Jazz: Research Funding; Kadmon: Research Funding; Kite: Research Funding; Pharmacyclics: Research Funding. Mannis:AbbVie, Agios, Bristol-Myers Squibb, Genentech: Consultancy; Glycomimetics, Forty Seven, Inc, Jazz Pharmaceuticals: Research Funding.

Background Angina pectoris (AP) is common in coronary artery disease (CAD), but whether those with diabetes mellitus (DM) experience AP as often as those without DM is unclear. Hypothesis AP prevalence is similar in those with vs without DM in a community sample with CAD. Methods In adults with CAD in the US NHANES 2001–2010, AP was determined by self-report and Rose questionnaire and compared by DM status. Physical functioning and medication use were also evaluated. Results Of 1957 adults with CAD, 619 (28.2%) had DM. Prevalence of AP was similar in those with vs without DM (48.9% vs 46.3%; P = 0.38). There was a trend toward more severe AP in those with glycated hemoglobin ≥7% (50.4%) vs

A 67-year-old male with past medical history of mantle cell lymphoma and atrial fibrillation presented with a truncal rash, bilateral lower extremity weakness, and confusion. Within three days of presentation, his condition rapidly deteriorated with the onset of diffuse flaccid paralysis, aphasia, and severe alteration in mental status. Initial results from serum studies, lumbar puncture, magnetic resonance imaging, and electroencephalogram were not diagnostic. However, on the ninth day after initial presentation, the West Nile Virus (WNV) immunoglobulin M antibody returned positive from the cerebrospinal fluid. West Nile Virus encephalitis is endemic worldwide, and is the most common viral encephalitis in the United States. WNV presents in a variety of ways, and the recognition by physicians is crucial due to the estimated 2- 12% mortality rate and significant longterm morbidity of neuroinvasive disease. The initial management and long term prognosis are points of ongoing research. This case represents a particularly profound example of neuroinvasive WNV. Our patient made a significant recovery after his initial presentation with aggressive supportive care, however still suffers from bilateral lower extremity weakness more than a year later.

Background: Oral 5-aminosalicylic acid (5-ASA) has proven an effective maintenance therapy of ulcerative colitis and may also be useful in Crohn's disease, but its safety in pregnancy has not been established. The present study therefore examined the course and outcome of pregnancies in patients with inflammatory bowel disease who continued to take oral 5-ASA. Methods: Ten patients with ulcerative colitis and 7 patients with Crohn's disease with a total of 19 pregnancies were studied while they were receiving 5-ASA. All patients were previously in remission on 5-ASA, at a mean dose of 1.7 g/day (range, 0.8–2.4 g/day). They continued taking the drug without a change in dose and were followed up throughout their pregnancies and postpartum. Results: Eighteen pregnancies resulted in full-term delivery. No fetal abnormalities were found at delivery, and there were no clinical or biochemical abnormalities in the neonatal period. Four patients had a relapse. One patient required a colectomy but carried on to a full-term pregnancy. One patient had a miscarriage, but she had miscarried on four previous occasions before taking 5-ASA. She subsequently had a successful pregnancy on 5-ASA. Conclusions: Oral 5-ASA appears to be safe for the management of inflammatory bowel disease during pregnancy.

The purpose of this book is to be a “Pretty Darned Quick” guide to the principles of evidence-based health care (EBHC) and to the use of healthcare databases to retrieve methodologically sound studies. The book targets health care professionals who might be interested in making EBHC decisions. The main author is a librarian, who shares her many years of experience and expertise as an information retrieval professional. McKibbon A, Eady A, Marks S. PDQ evidence-based principles and practice. Hamilton, Ontario, Canada: BC Decker Inc.; 1999. The text is organised by category of research. Individual chapters cover studies of therapy, diagnosis, aetiology, and prognosis. Systematic review articles, clinical practice guidelines, economic …