ALBERT

Description: Abstract 4742 Introduction While the distance patients travel to a treatment center (DTC) adversely impacts survival of patients with trauma, cardiac, or neurological disorders, as well as certain solid tumors, less is known of its influence in acute myeloid leukemia (AML). Care for patients with AML involves frequent emergent and urgent management, often complicating primary therapy provided in distant tertiary referral centers. We therefore hypothesized that increased DTC has a negative impact on outcome. We tested this hypothesis by assessing the effect of DTC on survival of patients with AML receiving care at a single institution. Patients and Methods Within the Stanford Leukemia Database, we identified 884 consecutive adult patients between 1993 and 2009 meeting the following criteria: age 〉=18, newly diagnosed AML (excluding APL), clinical management at Stanford University Medical Center (SUMC), and verified residence location available for DTC determination. Of these, 571 were deemed fit by the admitting physician to receive myelosuppressive induction chemotherapy. DTC was calculated by straight-line journey distance between home address at the time of diagnosis and treatment center. Results The median age for the entire cohort is 55 years and 322 patients (36%) are older than 60 years of age. Median survival for the entire cohort was 14.0 months. DTC was not univariately associated with outcome as a continuous variable. When testing for a critical DTC threshold impacting outcomes across the entire cohort, we found a significant correlation between longer DTC and adverse outcomes, shorter DTC was associated with lower OS. Patients living within 20 miles of SUMC had a worse median overall survival (10.4 months versus 15.0 months, HR 1.23, corrected p-value 0.02). However, when adjusted for administration of induction chemotherapy (p

Description: Abstract 3288 Introduction: The elderly constitute the majority of patients (pts) with AML. Effective and tolerable therapeutic alternatives are necessary for these pts, in whom outcomes with standard induction therapy are poor. Azacitidine (AZA), a DNA methyltransferase inhibitor, decreases methylation of tumor suppressor gene (TSG) promoters, which correlates with clinical responses. Lenalidomide (LEN), an immunomodulatory and anti-angiogenic agent, has anti-leukemic activity when used as a single agent. We hypothesized that combining these two agents would decrease promoter methylation and upregulate TSG expression. We present the Phase I results of a Phase I/II clinical trial that sequentially combines AZA with LEN in elderly, previously untreated AML pts. Methods: Eligible pts were ≥ 60 years, had a World Health Organization-confirmed diagnosis of non-M3 AML, a performance status (PS) ≤ 2, adequate organ function, no prior leukemia therapy and were not candidates for standard induction. All pts had a white blood cell count ≤ 10,000/mm3 at the time of study entry; the use of hydroxyurea to attain this was permitted. Pts were enrolled into 4 cohorts using a 3+3 dose escalation design. In cohort 1, pts received 75 mg/m2 AZA SC/IV on d 1–7, followed by 21 days of observation for a 28-day cycle. At the completion of this “cycle 0,” pts were escalated to cycle 1, in which they received the same dose and schedule of AZA followed by LEN 5 mg PO daily on d 8–28, and then observation on d 29–42. Cohorts 2, 3 and 4 received the same dose and schedule of AZA with LEN doses of 10, 25 and 50 mg respectively, at the same schedule described for cycle 1. Intra-cohort dose escalation after cycle 0 was not permitted. Baseline bone marrow biopsies were compared to biopsies obtained after cycles 0, 1, 3, 6 and 12, and response assessments were based on International Working Group criteria. Adverse events (AEs) were graded according to the NCI CTCAE v 3.0. Pts were eligible for a maximum of 12 cycles, provided they tolerated therapy and achieved a response (defined as a complete response [CR], a CR with incomplete recovery of blood counts [CRi] or a partial response [PR]). Result: Eighteen pts were enrolled between April 2009 and July 2010. The median age was 72 years (64-86), 67% were male and 94% were Caucasian. The median PS was 1 (0-2) and the median hematopoietic cell transplant comorbidity index score was 0.5 (0-4). Six of 18 (33%) required hydroxyurea prior to enrollment. Seven of 18 (39%) had de novo AML and 11/18 (61%) had secondary AML (1 therapy-related, 1 evolved from primary myelofibrosis and 9 with myelodysplasia-related changes). The median bone marrow blast percentage was 63.5% (21-91%). Three of 18 (17%) pts had adverse cytogenetics, while 15/18 (83%) pts exhibited intermediate grade cytogenetics (11/15 with normal karyotype). Grade 3 serious AEs with a suspected relationship to treatment included neutropenic fever (NF) (n=5), fatigue (n=3), renal insufficiency (n=2), hyponatremia (n=1) and bleeding (n=1). In Cohort 4, 1/6 pts experienced grade 4 NF; however, 5/6 did not experience DLT, and therefore, the MTD was not reached. Pts have completed a median of 2 treatment cycles (0-6), with a median follow up of 94 days (21-275). Presently, of the 17 evaluable pts, 9/17 (53%) are alive. The overall response rate (ORR; defined as CR+CRi+PR) is 8/17 (47%) and the CR+CRi rate is 4/17 (24%). Thirty-day mortality was 12% (2/17); both deaths occurred in the first cohort in pts who had not received the drug combination, and were related to disease progression. Of the 5 pts enrolled in cohort 1, none responded, and all ultimately died of disease progression. However, among those in cohorts 2–4, 9 of 12 (75%) evaluable pts are alive with an ORR of 67% (CR+CRi= 4/12 [33%]), a median of 104 days after initiation of treatment (42-275). No responder has relapsed to date. Of the 3 post-cohort 1 deaths, 1 was from disease progression and 2 were from infectious complications. Conclusion: The sequential combination of AZA and LEN was well tolerated in elderly, untreated AML pts. The MTD was not reached at the highest dosing cohort, and the Phase II dose and schedule is AZA 75 mg/m2 d 1–7 and LEN 50 mg d 8–28, on a 6-week cycle schedule. The preliminary ORR of 47% is encouraging, as is the 67% ORR in pts who received ≥10 mg of LEN. Six month follow up will be presented. This trial was registered at ClinicalTrials.gov as NCT00890929. Disclosures: Off Label Use: Azacitidine and lenalidomide for AML. Liedtke:Celgene: Lecture Fee, Research Funding.

Description: Background Asparaginase is an important component of induction and consolidation chemotherapy for acute lymphoblastic leukemia (ALL). Effective asparagine depletion in adult patients with ALL results in a longer duration of overall survival and disease free survival. Variation in asparaginase activity is in part due to the formation of anti-asparaginase antibodies that inactivate asparaginase and result in inadequate asparagine depletion. In addition, the presence of anti-asparaginase antibodies influences dexamethasone pharmacokinetics by increasing dexamethasone clearance, which has been shown to correlate with a higher risk of relapse. Hypoalbuminemia is a recognized side effect of asparaginase, and has been studied as a measure of asparaginase inhibition of liver protein synthesis. The purpose of this retrospective study was to evaluate the effect of asparaginase activity during induction, using serum albumin as a surrogate marker, on overall outcomes. We hypothesized that patients with lower albumin levels, and thus increased asparaginase activity, would have improved survival. Methods A retrospective electronic chart review was performed on 108 adult patients with newly diagnosed ALL who underwent induction chemotherapy treatment with Cancer and Leukemia Group B (CALGB) 9511 protocol at Stanford Hospital and Clinics between 2004 and 2012. PEG-asparaginase (2000 units per m2, capped at 3750 units) administration on day 5 of induction was confirmed on the electronic medical administration record. Patients also received therapy per protocol including prednisone (60mg per m2 per day) from days 1 through 21, with the exception of patients 〉60 years old who received prednisone from days 1 through 7. The primary outcomes measured were median overall survival and disease free survival. Patients were divided based on percent change in albumin level at day 14 of induction, using 20% decrease from pre-treatment baseline as a cut-off. The log rank test was used to calculate differences in survival and the Cox proportional hazards model was used to calculate hazard ratios. Baseline characteristics between the two groups were compared using chi-square or t-test analysis. Results A total of 104 patients with newly diagnosed ALL were included in the final analysis (1 patient did not receive PEG-asparaginase and 3 were lost early to follow-up). Of these, 52% were male. The median age was 49 years, and 20% of patients were 60 or older. The majority had B cell ALL (88%). Cytogenetics were normal in 28% of patients; t(9;22) was observed in 28% and t(4;11) in 4%. The induction mortality was 9% and 88% achieved complete remission (CR). In the entire patient population, the median overall survival was 27.4 months, and the median disease free survival was 25.0 months. For the patients who achieved at least a 20% decrease in albumin at day 14 of induction (57 patients), there was a statistically significant difference in median overall survival compared to those who had less than a 20% decrease in albumin, with an overall survival duration of 47.4 months and 15.8 months, respectively (HR = 2.23, P = 0.007). The median duration of disease free survival in those who achieved at least a 20% decrease in albumin at day 14 was 39 months compared to 13 months in those with less than a 20% decrease (HR = 1.93, P = 0.039). There was no statistically significant difference in the rate of CR between the two groups (P = 0.503). There was also no statistically significant difference in the baseline characteristics (age, WBC at diagnosis, presence of Philadelphia chromosome, and proportion of patients who eventually underwent BMT) between the two groups. Conclusion This study found a correlation between a decrease in albumin levels during induction, which was used as a surrogate measure of asparaginase activity, and duration of overall survival and disease free survival. This suggests that lower albumin levels associated with higher asparaginase activity and adequate asparagine depletion are important predictors of outcomes. Further studies assessing the effect of optimal individualized dosing of asparaginase based on albumin levels and/or asparagine depletion might be helpful to improve outcomes of adult patients with ALL. Disclosures: No relevant conflicts of interest to declare.

Description: Key Points Inactive prochemerin is activated in plasma by coagulation enzymes to active chemerin forms that are adipokines and chemoattractants. FXIa cleaves prochemerin, forming a partially active intermediate that is then fully activated by plasma basic carboxypeptidases.

Description: Introduction Thrombophilia diagnostics are frequently ordered in the inpatient hospital setting, but their impact on patient care is often equivocal. Thrombophilia testing is expensive, and many results are subject to confounding when ordered in the context of an acute hospitalization. Furthermore, these tests are frequently lost to follow-up or wastefully repeated after the patient is discharged. In this study, we conducted a retrospective chart review to determine the rate and financial impact of inappropriate thrombophilia test ordering across all inpatient services at Stanford Hospital over one calendar year. Methods Utilizing data from our finance department, we obtained a list of all inpatient thrombophilia testing ordered at Stanford Hospital from June 2014 through June 2015. Thrombophilia testing was defined as ordering any of the following: factor V Leiden, prothrombin G20210A mutation, antithrombin III, lupus anticoagulant, beta-2 glycoprotein 1 IgM/IgG, anticardiolipin IgM/IgG, dilute Russell viper venom time, protein C or protein S levels, and JAK2 V167F mutation. The criteria for defining a test as 'inappropriate' were guided by utilizing major society guidelines and current evidence, placing an emphasis upon the ordered tests' clinical relevance and reliability in the context of the patient's admission diagnosis. The criteria were formulated by a senior hematologist with specific expertise in thrombophilia evaluations. Two internal medicine resident physician data reviewers independently evaluated the ordered tests to determine their appropriateness. To ensure consistency between reviewers, identical test datasets were evaluated and compared, demonstrating satisfactory concordance (〉0.85). When the appropriateness of a test was unclear, joint evaluation was performed with the entirety of the study team to arrive at a final conclusion. Each test was linked to the ordering primary service. Charge data for each individual test was obtained through our financial department. Aggregate data were evaluated manually. Results In total, we reviewed 889 individual orders involving 167 patients across 20 ordering specialties. Of the 889 total orders, 331 were deemed inappropriate (37.2%), translating into a cumulative hospital charge of $152,923 (Figure 1). The tests most frequently inappropriately ordered included antithrombin III (94.4%), factor V Leiden (93.2%), protein C (92.7%), protein S (92.2%), and the prothrombin G20210A mutation (89.3%). Ordering individual tests in the setting of clearly provoked thrombotic events, during the acute thrombotic period, while patients were on concurrent anticoagulation, or when results failed to impact management represented the most common reasons testing was deemed inappropriate. Ordering practices were then stratified across the hospital's different primary services. Of services with the highest volume of test ordering, General Medicine (38.1%) and Neurology (34.9%) ordered testing inappropriately at the highest rates, while Rheumatology (12.8%) and Hematology (15.9%) ordered inappropriately at the lowest rates. Notably, the non-teaching services ordered testing inappropriately at one of the highest rates (62.2%), though their volume of ordering was lower in comparison with the aforementioned groups. Discussion Our results illustrate the high prevalence and significant financial impact of inappropriate or unnecessary thrombophilia testing conducted in the inpatient setting at our institution. Factors confounding test validity were frequently present at the time of ordering. Furthermore, stratifying ordering practices by specialty illustrated the differential rates of inappropriate ordering between services. Even when thrombophilia testing results fail to impact short term decision-making, misappropriated labeling of patients as 'thrombophilic' can have a lasting negative impact on future anticoagulation decisions. Combined with the high cost of errant ordering, these serve as a strong impetus to reduce the rate of thrombophilia testing during inpatient hospitalizations. Our baseline data demonstrate a need for institution-wide changes such as implementing electronic best practice advisories or potential ordering restrictions, and of tantamount importance, service-specific educational interventions in order to reduce unnecessary expenditures and improve patient care. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 4027 Background: Anthracyclines, such as doxorubicin, are effective and generally well tolerated when used in combination with bortezomib, thalidomide or lenalidomide (LEN) in multiple myeloma (MM). However, dose dependent cardiac toxicity is a limitation of anthracycline treatment. Amrubicin is a third generation anthracycline that is not associated with cardiac toxicity. No anthracyline-class related maximum cumulative dose of amrubicin has been established. Here we report the findings from the dose escalation portion of a phase I/II trial of amrubicin with LEN and dexamethsone (DEX) in patients with relapsed and/or refractory MM. Methods: The primary objectives were to establish the maximum tolerated dose (MTD) and toxicity profile for the combination of amrubicin with LEN and DEX. Secondary objectives were to determine the overall response rate, progression free survival (PFS), and time to tumor progression. Patients with MM who had received ≥1 prior therapy, which may have included lenalidomide and/or an anthracycline, were eligible. Patients received amrubicin beginning with 40 mg/m2 intravenously on Day 1, LEN 15 mg orally daily on Days 1 to 14, and DEX 40 mg orally on Days 1, 8 and 15 of each 21 day cycle. Dose escalation of amrubicin proceeded using a standard 3+3 schema based on dose limiting toxicities (DLTs) occurring in cycle 1. There were 3 planned dose cohorts: 40 mg/m2, 60 mg/m2, and 80 mg/m2. Pegfilgrastim 6 mg was administered subcutaneously on Day 2. Prophylactic anticoagulation with aspirin or low molecular weight heparin was mandatory. Maximum treatment period was 4 cycles in the absence of unacceptable toxicity or disease progression as assessed after a minimum of 2 cycles. Patients who achieved a response or stable disease after 4 cycles continued on maintenance with LEN with or without DEX until disease progression or until toxicity occurred. Adverse events (AEs) were graded by NCI-CTCAE v4. Response was assessed by current IMWG criteria. Results: Ten patients have been enrolled to date (cutoff: August 10, 2012). The MTD has not been reached. Currently patients are enrolling in the third and final dose cohort, which is receiving amrubicin 80 mg/m2. Patients had a median age of 62.5 years (range 51–77), and median ECOG performance status of 1. Nine patients had refractory disease at the time of enrollment, including 7 refractory to LEN. Nine patients were previously treated with a proteasome inhibitor, and 9 patients with an immunomodulator. Three patients had undergone autologous hematopoietic stem cell transplant (HSCT); 1 of these patients also underwent allogeneic HSCT. All patients had lytic bone lesions, and 7 patients had 4 or more lesions. One patient had high risk cytogenetics with a p53 mutation. Median cardiac ejection fraction was 59% at baseline. Patients received a median of 2 treatment cycles (range 1–4). Median follow up time was 3.25 months (range 0.25–11.75). Most commonly reported treatment related AEs included grade 1 GI symptoms such as dysguesia, anorexia, nausea, emesis, diarrhea, and constipation. One patient experienced grade 3 neutropenia, and 2 patients experienced grade 3 anemia. One patient was taken off study during cycle 1 due to reactivation of oral GVHD. One patient in the 3rd cohort was taken off study during cycle 1 due to DLTs, including grade 3 dizziness and diarrhea for 7 days. Cardiac ejection fractions were unchanged in all patients after completing treatment. No cardiac or thromboembolic events occurred. Five patients were evaluable for treatment response. Three patients completed 4 cycles of treatment; 1 patient had a partial response to treatment and went on to maintenance with LEN and DEX; 2 patients had stable disease on treatment, and elected not to continue maintenance. The remaining two patients had stable disease; one discontinued treatment after 2 cycles to pursue other treatment, the other discontinued treatment after 3 cycles in order to receive radiation therapy for pain management of lytic bone lesions. Median PFS for all patients was 4.25 months (range 0.75-NR). Median time to next treatment after discontinuing study drug was 1 month (range 0.25–5). Conclusions: These data suggest that amrubicin in combination with lenalidomide and dexamethasone is overall well tolerated in this heavily pre-treated population. To date, toxicity has been manageable, and no cardiac toxicity has been observed. Disclosures: Liedtke: Celgene: Research Funding.

Description: Abstract 3313 Introduction: Temozolomide sensitivity is determined by the methylation status of the MGMT promoter. As most AML patients have an unmethylated MGMT promoter, response rates to temozolomide have been very disappointing in the past. We designed this exploratory study to determine whether temozolomide therapy can be tailored according to the MGMT promoter status and to test the hypothesis that protracted, low-dose temozolomide can “prime” leukemia blasts to conventional doses of temozolomide in patients with unmethylated MGMT promoter. Patients and Methods: Elderly patients (〉60 years of age) with AML and high-risk features (relapsed/refractory, secondary AML or de novo with intermediate or unfavorable cytogenetics) were stratified according to MGMT promoter methylation status. Patients with methylated MGMT promoters received temozolomide 200mg/m2 orally for 7 days, while patients with unmethylated promoters received temozolomide 100mg/m2 orally for 14 days followed by temozolomide 200mg/m2 orally for 7 days. Results: 36 patients (median age, 75 years) were treated with temozolomide and 31 (86%) were found to have an unmethylated MGMT promoter. Overall response rate for the entire cohort was 36% (CR – 22%, CRp – 8%, LFS- 6%). The median duration of response and median overall survival among responding patients were 29 weeks and 35 weeks, respectively. No differences in outcomes (CR rate, OS rate and duration of remission) were noted among the 2 stratification groups (Table-1) Induction deaths (within 42 days of treatment initiation) occurred in 25% (9/36) of patients and were mostly caused by disease progression. Patients with low HCT-CI scores (≤ 2) had higher ORR 43% vs.0%, fewer induction deaths (17% vs. 67%, respectively) and longer median OS (94 days vs. 25.5 days). Hematological toxicities were the most commonly observed adverse events and difficult to distinguish from disease-related cytopenias. Conclusion: Temozolomide therapy, stratified according to MGMT promoter methylation status, demonstrated clinical activity in elderly patients with AML and high-risk features. Protracted low-dose temozolomide may reverse the temozolomide-resistant phenotype in patients with unmethylated MGMT promoters. Future studies in better-defined populations or in combination are warranted. This trial was registered at ClinicalTrials.gov as NCT00611247. Disclosures: Medeiros: Schering-Plough: Research Funding. Off Label Use: Temozolomide for elderly AML.

Description: Abstract 4304 Background Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells accompanied by end organ damage. Although cytotoxic chemotherapy including high dose chemotherapy with stem cell support have improved survival of symptomatic patients, all patients invariably relapse. For patients with relapsed disease further chemotherapy is generally of limited benefit, indicating the need for novel therapies. Pralatrexate is a folate antagonist which has been FDA approved for the treatment of peripheral T-cell lymphoma. It has been shown to be safe in combination with various cytotoxic agents. In preclinical studies, pralatrexate has been shown to be synergistic with the proteosome inhibitor bortezomib. This phase I/II study is being conducted with the support of the NCCN to determine the safety and maximum tolerated dose (MTD) of pralatrexate in combination with bortezomib in the treatment of relapsed/refractory MM. Methods The primary objectives were to determine the MTD and recommended phase II dose and toxicity profile of pralatrexate in combination with bortezomib. The secondary objectives were to determine clinical evidence of anti-myeloma activity based on response criteria of the International Myeloma Working Group Uniform Response Criteria (IMWGURC). Additionally, anti-tumor activity was measured by duration of response (DOR), progression free survival (PFS), and overall survival (OS). Eligible patients were age 〉18, with measurable MM that had relapsed following, or was refractory to at least 1 previous treatment. Refractoriness to bortezomib was allowed. Patients received pralatrexate intravenously on days 1, 8 & 15 in 3-dose cohorts of 10, 20 or 30 mg/m2 and bortezomib intravenously on days 1, 8 & 15 at a fixed dose of 1.3 mg/m2. Patients took folic acid 1mg daily as well as intramuscular vitamin B12 every 8–10 weeks. A standard 3+3 dose escalation was used for determining the MTD. In this study, dose-limiting toxicity (DLT) was determined during cycle 1 and defined as grade 3 febrile neutropenia, grade 3 or grade 4 non-hematologic treatment-related toxicity, or treatment delays exceeding 14 days in the first cycle of treatment. A maximum of 4 28-day cycles was planned. Results Nine patients with a median age of 60 (55–74 years) have been enrolled on the study to date. The MTD has not been reached. Patients are currently enrolled in the 3rddose cohort. The median number of previous therapies was 2 (range 1–4). Eight pts (88%) had received previous treatment with bortezomib, and 8 with immunomodulatory agents. Two patients had undergone autologous transplant. Six patients had refractory disease, including 5 refractory to bortezomib. Seven patients had bony disease, including 5 (55%) with 〉3 lesions. FISH studies revealed 2 patients with monosomy 13 and one with a p53 deletion. Patients received a median of 2 treatment cycles (range 1–4). The median follow-up time is 12.4 months (range 0.46–22.9). To date, the most common grade 3 or 4 adverse events occurring in more than 10% of patients, were thrombocytopenia (66%) and neutropenia (22%). Grade 3 mucositis was observed in 1 patient and constituted a DLT. Subsequent patients were given leucovorin to take at the first sign of mucositis. One patient had a grade 3 shingles infection. Of the eight patients evaluable for response, 2 achieved a partial response, 5 had stable disease, and 1 progressed. The median duration of response was 46 days (range 38–54). After completion of the study 1 patient started maintenance, and 7 patients started alternative therapy including transplant in 3 patients. The median time to next treatment was 23 days (range 13–196). There were no deaths on the study. The median PFS was 7.6 months (range 0.4–18.8). The median OS was 12.4 months (range 0.4–22.9) Conclusions The combination of pralatrexate 30mg/m2 and bortezomib 1.3mg/m2 on days 1, 8, and 15 appears to be a safe treatment option for heavily pre-treated patients with multiple myeloma. The main toxicities of this regimen are thrombocytopenia and mucositis. Disclosures: Liedtke: Millennium: Research Funding.

Description: 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.