Citations

Background and Aims Vascular invasion (VI) is a critical risk factor for HCC recurrence and poor survival. The molecular drivers of vascular invasion in HCC are open for investigation. Deciphering the molecular landscape of invasive HCC will help identify therapeutic targets and noninvasive biomarkers. Approach and Results To this end, we undertook this study to evaluate the genomic, transcriptomic, and proteomic profile of tumors with VI using the multiplatform cancer genome atlas (The Cancer Genome Atlas; TCGA) data (n = 373). In the TCGA Liver Hepatocellular Carcinoma cohort, macrovascular invasion was present in 5% (n = 17) of tumors and microvascular invasion in 25% (n = 94) of tumors. Functional pathway analysis revealed that the MYC oncogene was a common upstream regulator of the mRNA, miRNA, and proteomic changes in VI. We performed comparative proteomic analyses of invasive human HCC and MYC‐driven murine HCC and identified fibronectin to be a proteomic biomarker of invasive HCC (mouse fibronectin 1 [Fn1], P = 1.7 × 10 −11 ; human FN1, P = 1.5 × 10 −4 ) conserved across the two species. Mechanistically, we show that FN1 promotes the migratory and invasive phenotype of HCC cancer cells. We demonstrate tissue overexpression of fibronectin in human HCC using a large independent cohort of human HCC tissue microarray (n = 153; P < 0.001). Lastly, we showed that plasma fibronectin levels were significantly elevated in patients with HCC (n = 35; mean = 307.7 μg/mL; SEM = 35.9) when compared to cirrhosis (n = 10; mean = 41.8 μg/mL; SEM = 13.3; P < 0.0001). Conclusions Our study evaluates the molecular landscape of tumors with VI, identifying distinct transcriptional, epigenetic, and proteomic changes driven by the MYC oncogene. We show that MYC up‐regulates fibronectin expression, which promotes HCC invasiveness. In addition, we identify fibronectin to be a promising noninvasive proteomic biomarker of VI in HCC.

Abstract Prior in vitro work in the human hepatoma cell lines Huh7 and HEP3B indicated that combination treatment of the BH3 mimetic, navitoclax, and the multi-kinase inhibitor, sorafenib, was more effective at inducing apoptosis than either compound alone. This current study was part of a phase I clinical trial to determine the maximum tolerated dose of concurrent navitoclax and sorafenib treatment in patients with relapsed or refractory solid organ tumors and sought to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of both agents in combination. Cleavage of cytokeratin 18 by caspase 3 was used as a biomarker for therapy-induced activation of apoptosis to determine if combination treatment results in an increase in apoptosis as previously observed in in vitro work. PK were assessed in 26 patients (ages 32 - 80) enrolled in a phase I clinical trial (NCT02143401). 150 mg of oral navitoclax was administered once daily for a seven day run-in (beginning Day -7) prior to 150 mg (Dose level 1) or 200 mg (Dose level 2) navitoclax concomitant treatment with 400 mg of twice daily oral sorafenib (Day 1). Samples for pharmacokinetic analysis were obtained on Day -7 and Day 1 prior to dosing and at 1, 2, 4, 8-12, and 24 hours post dosing. PK parameters were estimated by noncompartmental analysis using Phoenix® WinNonlin® Version 6.4. To examine the PD of both agents in combination, cytokeratin 18 cleavage was quantified by ELISA after the 7-day navitoclax run-in and on Day 2 or 4 and Day 8 of navitoclax and sorafenib combination treatment. PK estimates of maximum concentration, exposure, volume of distribution, and clearance for navitoclax on Day -7 and Day 1 were not significantly different, indicating a lack of navitoclax accumulation. Finally, no correlation was found between navitoclax exposure and apoptosis as indicated by cytokeratin-18 cleavage. This work was supported by the NCI Cancer Center Support Grant P30 CA15083 and NCI Experimental Therapeutics Phase I Grant UM1 CA186686. Citation Format: Emily J. Koubek, Brian A. Costello, Jun Yin, Renee M. McGovern, Sarah A. Buhrow, Renee A. Schoon, Carrie A. Strand, Yixing Jiang, Mitesh J. Borad, Naoko Takebe, Scott H. Kaufmann, Alex A. Adjei, Joel M. Reid. Pharmacokinetic analysis of navitoclax in combination with sorafenib in patients with relapsed or refractory solid organ tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT114.

Abstract Background It is unclear whether results from recent trials of resectable pancreatic ductal adenocarcinoma (PDAC) are generalizable to older patients, who are underrepresented. We aimed to evaluate outcomes of surgery and of neoadjuvant and adjuvant therapy in older patients with resectable PDAC. Patients and Methods We included patients aged ≥65 years with upfront resectable PDAC from a prospectively maintained pancreatic cancer registry from 2007 to 2016. Patients were stratified into ages 65–75 and 75+ years. Overall survival (OS) was assessed in treatment comparisons: (A) surgery (n = 636) versus nonsurgical (n = 178), (B) neoadjuvant therapy (n = 139) versus upfront surgery (n = 497), and (C) adjuvant therapy (n = 379) versus surgery alone (n = 118). We compared neoadjuvant (n = 139) versus adjuvant therapy (n = 379) in an exploratory analysis. Results Nine hundred and three patients had a median age of 73.7 (range, 65–96.6) years. Median OS was 26.6 versus 11.9 months (adjusted hazard ratio [HRadj], 0.4; 95% confidence interval [CI], 0.31–0.52; p &lt; .001) in Comparison A groups, 30.7 versus 25.8 months (HRadj, 0.69; 95% CI, 0.49–0.96; p = .03) in Comparison B groups, and 26.9 versus 17.4 months (HRadj, 0.62; 95% CI, 0.44–0.88; p = .008) in Comparison C groups, respectively. OS benefit in these treatment comparisons was present in age group 75+ with HRadj 0.24 (95% CI, 0.16–0.36; p &lt; .001) in Comparison A and HRadj 0.52 (95% CI, 0.27–1; p = .049) in Comparison B, but not in Comparison C with HRadj 0.68 (95% CI, 0.43–1.08; p = .1). Statistically comparable median OS of patients who received neoadjuvant or adjuvant therapy stratified by age groups was observed. Conclusion Older patients with resectable PDAC who received surgery, neoadjuvant therapy, or adjuvant therapy appeared to have improved survival outcomes compared with those who did not receive such treatment. Implications for Practice Older patients with resectable pancreatic ductal adenocarcinoma (PDAC) in general are underrepresented in large clinical trials and less well studied in terms of the role of surgery, neoadjuvant therapy, and adjuvant therapy. This study collected data on older patients with resectable PDAC from a prospectively maintained single-institutional pancreatic cancer registry of a tertiary referral center from 2007 to 2016. It was found that, with multidisciplinary evaluation, older patients with resectable PDAC who received surgery, neoadjuvant therapy, or adjuvant therapy appeared to have improved survival outcomes compared with those who did not receive such treatment. These results are of substantial importance to practitioners who treat older patients, who are traditionally underrepresented in most clinical trials.

8038 Background: Bone marrow biopsies (BMB) are performed pre/post therapy to confirm complete response (CR) in patients (pts) with lymphoma on clinical trials. We evaluated 2 prior data sets and concluded that BMB impact response assessment in a minority of pts with follicular lymphoma (FL) (Rutherford BJH 2017; Rutherford ASH abstract 1605, 2018). We sought to establish if BMB add value in assessing response or identify distinct progression free (PFS) or overall survival (OS) outcomes in a large, multicenter, multi-trial cohort. Methods: Data were pooled from 7 trials of 580 pts with untreated FL conducted through the Alliance for Clinical Trials in Oncology and SWOG from 2002-2016. The proportion of pts with positive (+) baseline BMB, CR on imaging after treatment, and (+) repeat BMB was calculated using total pts enrolled as the denominator. We tested against the null hypothesis that the proportion was = 10%, the threshold below which BMB would be considered irrelevant for response assessment, versus (vs) the alternative hypothesis that this proportion was < 10%, using 1-sided exact binomial test. Response criteria were CT-based. Imaging was not used to assess BM involvement. Because confirmatory BMB were not completed in all indicated pts, landmark survival analyses compared PFS/OS of pts with CR on imaging and negative (-) BMB vs pts with CR on imaging without repeat BMB. Pts with CR on imaging were categorized as having (-) repeat BMB or no repeat BMB within 60 days of first CR on imaging. PFS and OS were calculated from time of first CR and estimated using Kaplan-Meier and Cox models adjusting for age, sex, stage, Follicular Lymphoma International Prognostic Index (FLIPI) score, and treatment type (targeted vs chemotherapy plus targeted therapy), and stratified by treatment arm. Results: Median age was 55 with 51% male, 96% stage III-IV, and 88% grade I-II. FLIPI scores were 113 low, 265 intermediate, and 199 high risk. 67% received chemotherapy-based regimens. Baseline BMB was (+) in 321 (55%). Only 5/580 (0.8%) had (+) baseline BMB, CR on imaging, and subsequent (+) BMB (p < 0.0001). Of pts with CR on imaging, PFS and OS were not different among pts with (-) BMB vs pts without repeat BMB (PFS: HR = 1.08, 95%CI 0.61-1.93, p = 0.783; OS: HR = 0.52, 95%CI 0.20-1.40, p = 0.199). Conclusions: BMB requirements may discourage pt participation in trials and add pain, expense and time without providing necessary information. We recommend eliminating BMB for response assessment from FL clinical trials. Clinical trial information: NCT00553501, NCT01145495, NCT01190449, NCT01286272, NCT01829568, NCT00822120, and NCT00770224 .

Objectives: Survival benefit of combination over single-agent chemotherapy for metastatic pancreatic ductal adenocarcinoma (PDAC) was demonstrated in younger patients in clinical trials. The authors aimed to evaluate whether this survival benefit of combination chemotherapy is present in elderly patients with metastatic PDAC. Materials and Methods: The authors identified elderly patients (age 65 y or older) with stage IV PDAC and extracted available clinical information from a prospectively maintained institutional pancreatic cancer registry from 2007 to 2016. The primary endpoint was overall survival. Cox proportional hazards regression was used for multivariable survival analyses. Survival outcomes for the entire cohort and by age group I (elderly, 65 to 75 y) and age group II (very elderly, older than 75 y) were assessed. Results: A total of 606 patients were included with a median age of 73.8 years. Among them, 239 patients (39%) received combination chemotherapy and 152 patients (25.1%) received single-agent chemotherapy as first-line treatment. Combination chemotherapy was associated with significantly longer median overall survival compared with single-agent chemotherapy (10.9 vs. 7.5 mo, P<0.001) with hazard ratio 0.62 (95% confidence interval, 0.47-0.81; P=0.001) after adjusting for age, sex, comorbidity, Eastern Cooperative Oncology Group (ECOG) performance status, and carbohydrate antigen 19-9 level. Analyses by age groups indicated that very elderly patients (age group II) benefited from combination chemotherapy compared with single-agent chemotherapy with hazard ratio 0.56 (95% confidence interval, 0.31-1; P=0.049), comparable with the age group I (P age-treatment interaction=0.81). Conclusion: Elderly patients, even those older than 75 years, with metastatic PDAC benefited from combination chemotherapy.

Abstract Background Carcinoembryonic antigen (CEA) levels are used in conjunction with imaging to monitor response to systemic therapy in metastatic colorectal cancer (mCRC). We sought to identify a threshold for CEA change from baseline to predict progressive disease (PD) in mCRC patients receiving first-line therapy. Methods Patients from trials collected in the ARCAD database were included if baseline CEA was at least 10 ng/mL and repeat CEA was available within 14 days of first restaging scan. Optimal cutoffs for CEA change were identified by receiver operating characteristic analysis. Prediction performance of cutoffs was evaluated by sensitivity, specificity, and negative predictive value. Analyses were conducted by treatment class: chemotherapy alone, chemotherapy with anti-VEGF antibody, and chemotherapy with anti-EGFR antibody. Results A total of 2643 mCRC patients treated with systemic therapy were included. Median percent change of CEA from baseline to first restaging for patients with complete response, partial response, or stable disease (non-PD) and PD was −53.1% and +23.6% for chemotherapy alone (n = 957) and −71.7% and −45.3% for chemotherapy with anti-VEGF antibody (n = 1355). The optimal area under the curve cutoff for differentiating PD from non-PD on first restaging was −7.5% for chemotherapy alone and −62.0% for chemotherapy with anti-VEGF antibody; chemotherapy alone, adjusted odds ratio = 6.51 (95% CI = 3.31 to 12.83, P &lt; .001), chemotherapy with anti-VEGF antibody, adjusted odds ratio = 3.45 (95% CI = 1.93 to 6.18, P &lt; .001). A 99% negative predictive value clinical cutoff for prediction of non-PD would avoid CT scan at first restaging in 21.0% of chemotherapy alone and 16.2% of chemotherapy with anti-VEGF antibody–treated patients. Among patients with stable disease on first restaging, those with decreased CEA from baseline had statistically significantly improved progression-free and overall survival. Conclusions Change in CEA from baseline to first restaging can accurately predict non-progression and correlates with long-term outcomes in patients receiving systemic chemotherapy.

188 Background: Unplanned subgroup analyses from several studies have suggested primary tumor sidedness (PTS) as a potential prognostic and predictive parameter in metastatic colorectal cancer (mCRC). We aimed to investigate the prognostic and predictive impact of PTS on outcomes. Methods: PTS data of 7,828 mCRC patients (pts) from 10 first-line randomized trials in the ARCAD database were pooled. PTS was defined as right-sided (RS) or left-sided (LS) if tumor arose from the cecum to the hepatic flexure or from the splenic flexure to the rectum, respectively; transverse colon cancers were not included. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for age, sex, performance status (PS), prior radiation/chemo, and stratified by treatment arm. Predictive value was tested by interaction term between PTS and treatment (anti-EGFR plus chemotherapy vs. chemotherapy alone). Results: Compared to RS pts (2407, 31%), LS pts (5421, 69%) had better OS (median: 21.6 v 16.8 mos; HRadj: 0.73, 95% CI 0.69-0.78, P < .001) and PFS (median 8.4 v 7.2 mos; HRadj: 0.81, 95% CI 0.76-0.86, P < .001). Results were consistent among subgroups defined by age, sex, PS, metastatic sites and chemo backbone (irinotecan- and oxaliplatin-based). Interaction between PTS and KRAS mutation was significant (Pinteraction< .001): LS is associated with better prognosis only among KRAS wild-type (wt) (HRadj: OS 0.62, 95% CI, 0.55-0.70; PFS 0.71, 95% CI 0.63-0.80), but not among KRAS mutated pts. Among KRAS wt pts, survival benefit from anti-EGFR was observed for LS, but not for RS (table). Conclusions: The prognostic value of PTS is restricted to the KRAS wt population. PTS is predictive of anti-EGFR efficacy, with a significant improvement of survival for LS mCRC pts. These results suggest treatment stratification in mCRC studies by both PTS and KRAS status. [Table: see text]

Uproleselan (GMI-1271) is a novel antagonist of E-selectin, an adhesion molecule expressed on endothelial cells. E-selectin is expressed transiently in the normal vasculature during an inflammatory response and constitutively in the bone marrow (BM). Binding of E-selectin (E-sel) to sialyl Lex, the E-sel ligand (E-sel-L), on the leukemic cell surface activates cell survival pathways and promotes chemotherapy resistance in AML. In preclinical models, blockade of E-selectin with uproleselan disrupts the activation of cell survival pathways and enhanced the efficacy of chemotherapy across multiple AML tumor models. Furthermore, uproleselan protected against chemotherapy-induced mucositis by regulating macrophage trafficking to the site of injury in the gut lining. A previous phase I/II study of uproleselan added to chemotherapy in patients with untreated AML (older adults ≥60 yrs) and relapsed/refractory AML (≥ 18yrs) showed promising remission rates (CR/CRi) and survival outcomes, and reduced rates of mucositis. In the newly diagnosed older patients, high remission rates were achieved overall (CR/CRi 72%) and for the high risk subgroup with sAML (CR/CRi 69%). In this phase 2/3 study, we will test the addition of uproleselan to a standard daunorubicin/cytarabine regimen in older adults with previously untreated AML. The study will enroll patients age ≥ 60 yrs with untreated acute myeloid leukemia. Patients with acute promyelocytic leukemia, activating mutations in FLT3, or evidence of central nervous system involvement are excluded. Subjects are randomized to 7+3 induction (cytarabine + daunorubicin) +/- uproleselan. Subjects achieving a CR/CRi may receive up to 3 cycles of consolidation with intermediate dose cytarabine 2 gm/m2 IV d1-5 +/- uproleselan. The primary phase II objective is to compare the event-free survival (EFS). A sample size of 262 patients was selected for the phase II to detect an improvement in median EFS from 7 months to 11 months (HR= 0.64) with &gt; 95% power, using a log rank test. The phase III primary objective will compare overall survival (OS). For the phase III, a sample size of 335 evaluable patients per arm (670 total inclusive of patients enrolled in phase II) will provide &gt;90% power to detect an improvement in median OS from 12 months to 16 months (HR= 0.75), using a log-rank test. Correlative studies will measure E-selectin ligand on AML blasts and soluble E-selectin and will also measure minimal residual disease after remission induction by multiparameter flow cytometry. A comprehensive geriatric assessment will identify baseline measures associated with EFS and develop a risk model to predict OS among older adults receiving intensive AML therapy. The study is endorsed by SWOG and ECOG-ACRIN and opened to enrollment on 1/16/2019. Figure Disclosures Uy: Astellas: Consultancy; Pfizer: Consultancy; Curis: Consultancy; GlycoMimetics: Consultancy. Dinner:Agios: Consultancy; Pfizer: Consultancy; AstraZeneca: Consultancy. Strickland:Jazz: Consultancy; Sunesis Pharmaceuticals: Research Funding; Pfizer: Consultancy; Kite: Consultancy; Astellas Pharma: Consultancy; AbbVie: Consultancy. Liesveld:Onconova: Other: Data safety monitoring board; Abbvie: Membership on an entity's Board of Directors or advisory committees. Byrd:Acerta: Research Funding; Acerta: Research Funding; Genentech: Research Funding; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; BeiGene: Research Funding; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; BeiGene: Research Funding; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; BeiGene: Research Funding; Novartis: Other: Travel Expenses, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; Genentech: Research Funding; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Acerta: Research Funding; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; Ohio State University: Patents & Royalties: OSU-2S; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau. Stone:Argenx, Celgene, Takeda Oncology: Other: Data and Safety Monitoring Board/Committee: ; AbbVie, Actinium, Agios, Argenx, Arog, Astellas, AstraZeneca, Biolinerx, Celgene, Cornerstone Biopharma, Fujifilm, Jazz Pharmaceuticals, Amgen, Ono, Orsenix, Otsuka, Merck, Novartis, Pfizer, Sumitomo, Trovagene: Consultancy; Novartis, Agios, Arog: Research Funding. OffLabel Disclosure: Uproleselan in AML

Abstract Dasatinib with corticosteroid yields high complete remission (CR) rates in Ph+ ALL with minimal induction death. Optimal post-remission therapy is not known. We report a prospective study evaluating dasatinib/dexamethasone induction then consolidation with reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), autologous HCT (autoHCT), or chemotherapy alone (chemo), followed by dasatinib-based maintenance. Methods: We conducted a phase II, 3-arm, non-randomized trial (NCT01256398, Support: U10CA180821, U10CA180882, U10CA180861, U24CA196171) at 17 US centers with primary objectives to determine 3-year overall survival (OS) and disease-free survival (DFS) of adults ≥18 years (yrs) old with untreated Ph+ ALL treated with dasatinib/dexamethasone induction, CNS prophylaxis with systemic and intrathecal methotrexate, consolidation with alloHCT, autoHCT, or chemo, then dasatinib maintenance. Induction (Course I) used dasatinib 140 mg orally daily and dexamethasone 10 mg/m2/day orally or IV days 1-7. If ≤20% lymphoblasts in marrow at Day 15, Course II continued dasatinib with 7 days of dexamethasone. If >20% lymphoblasts, patients (pts) also received vincristine and daunorubicin. Pts not in CR/CRi received a second induction (Course III) with dasatinib, cyclophosphamide, vincristine, daunorubicin, and dexamethasone. CNS prophylaxis (Course IV) used dasatinib, IV vincristine and IV, oral, and intrathecal methotrexate. Course V consisted of HCT or chemo. Pts 18-70 yrs old underwent RIC alloHCT if they had a HLA-matched donor; otherwise they underwent autoHCT. AlloHCT conditioning used fludarabine 30 mg/m2/day IV day -7 through -3, alemtuzumab 20 mg/day IV day -7 through -3, and melphalan 140 mg/m2 IV once on day -2. GVHD prophylaxis with tacrolimus began day -2. Pts undergoing autoHCT received etoposide 10 mg/kg/day (age >65, 5 mg/kg/day) CIV for 4 days and cytarabine 2 g/m2 (age >65, 1 g/m2) IV every 12 hours for 8 doses then G-CSF for mobilization. AutoHCT conditioning was melphalan 100 mg/m2/day IV on days -2 and -1. Pts >70 yrs old or unable to undergo HCT received etoposide/cytarabine alone. Dasatinib maintenance (Course VI) began day 30 of Course V and continued for 12 months and until 2 consecutive negative BCR-ABL1 RT-PCR assays 3 months apart or relapse. BCR-ABL1 isoform and ABL1 kinase domain (KD) mutation determination were done locally. Results: From 12/15/2010 to 11/14/2014, 64 eligible pts enrolled. Median age was 60 yrs (22-87); median WBC 23.2 x 103/μl (0.3-454). The dominant BCR-ABL1 isoform was p190 in 59%, p210 in 17%, and not reported in 23%. The CR rate was 97% with no induction deaths. Fifty-five pts completed CNS prophylaxis (Course IV). Twenty pts underwent protocol-specified alloHCT, 7 autoHCT, and 9 chemo. Nine pts underwent off-study alloHCT and 5 skipped Course V. Dasatinib maintenance was tolerable with 72%, 80%, and 80% receiving >50% of planned maintenance doses in alloHCT, autoHCT, and chemo arms, respectively. With a median follow up of 48 months (37-78) for survivors, 3-yr OS and DFS were 55% (median OS 45 months) and 43% (median DFS 30 months), respectively. For pts undergoing consolidation with protocol-specified alloHCT, autoHCT, or chemo, 3-yr OS was 75%, 71%, and 55% respectively with median OS not reached (NR) for all groups. DFS at 3-yrs was 55%, 43%, and 46% respectively. Median DFS for alloHCT was 42 months vs 15 months for autoHCT and 34 months for chemo (Log-Rank P=0.4). Outcomes were similar with inclusion of off-study alloHCT and chemo patients skipping Course V. Relative to p190 BCR-ABL1 isoform, p210 was associated with shorter median OS (NR vs 16 months, P=0.04) and median DFS (35 months vs 10 months, P<0.0001). Three-year DFS was 9% with p210. Relapse occurred in 23 pts with 5 CNS relapses reported, one isolated. Relapse occurred in 25% of alloHCT, 43% of autoHCT, and 37% of chemo pts. T315I mutation in ABL1 KD was detected in 6 of 8 marrow relapses (75%). One isolated CNS relapse had no ABL1 KD mutations. Conclusions: Dasatinib and dexamethasone followed by alloHCT, autoHCT, or chemo yield similar 3-yr survival comparable to approaches using intensive induction chemotherapy. Pts with the p210 BCR-ABL1 isoform had dismal outcomes and may benefit from alternate approaches. T315I mutation was the major cause of relapse and should be addressed in future studies. Disclosures Wieduwilt: Amgen: Research Funding; Reata Pharmaceuticals: Equity Ownership; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Leadiant: Research Funding; Shire: Research Funding; Merck: Research Funding. Uy:GlycoMimetics: Consultancy; Curis: Consultancy. Powell:Rafael Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Kolitz:Magellan Health: Consultancy, Honoraria. Liedtke:Caelum: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen/Onyx: Consultancy, Honoraria, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; celgene: Research Funding; Genentech/Roche: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BlueBirdBio: Research Funding. Stock:Jazz Pharmaceuticals: Consultancy. Devine:Kiadis Pharma: Consultancy. Larson:BristolMyers Squibb: Consultancy, Research Funding; Ariad/Takeda: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding.