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Abstract Background Therapy-related myeloid neoplasm (tMN) includes t-myelodysplasia (tMDS) and t-acute myeloid leukemia (tAML) and are serious late effects of the treatment of cancer. Prognosis of tMN is poor, related to the increased frequency of adverse cytogenetics and other clinical features which predict poor response to conventional treatment. Over the last years, azacitidine (AZA) has become the standard of treatment for high risk MDS (Silverman, JCO 2002; Fenaux, Lancet Oncol 2009) and has shown efficacy in AML. AZA represents an interesting option for patients with tMN considering its safety profile and its efficacy in poor prognosis subgroups of apparently de novo MDS patients including those with monosomy 7. Most prospective trials of AZA have excluded patients with tMN. Most tMN data are retrospective or registry studies (Bally, Leuk Res 2013). This abstract presents the results of 47 t-MN patients prospectively enrolled as a specific cohort in the E1905 study. Methods E1905 study is a randomized phase 2 study from the North American Leukemia Intergroup (NCT00313586, Prebet , ASH 2010) testing 10 days of AZA (50mg/m2/d s.c.) vs. 10 days of AZA + the histone deacetylase inhibitor entinostat (4 mg/m2/d PO days 3 and day 10). 6 cycles of treatment were planned; responding patients could receive up to 24 cycles. MDS, CMML, and AML with myelodysplasia-related changes were included. Patients with tMN were subsequently accrued as a separate cohort after amendment of the protocol. Response was assessed using IWG 2000 criteria (Cheson et al, Blood 2000); the primary endpoint of the overall trial was achievement of a normal hemogram in 25% of treated patients in either treatment arm. Results A total of 47 patients were included. Median age was 70 years (39y-83y), 45% male, and 94% of patients had ECOG PS 0-1. 29 patients could be subclassified as t-MDS and 18 as t-AML. At inclusion, median peripheral blood counts were: neutrophils 1.0 G/l, Platelets 35 G/L, Hemoglobin 9.2 g/l, peripheral blood blasts 0%, marrow blasts 14.0%. 68% of patients were RBC transfusion dependent and 40% platelet transfusion dependent. As expected, the cytogenetic evaluation showed a high frequency of unfavorable risk cytogenetics (74%) as compared to normal or intermediate risk cytogenetics (26%). Baseline characteristics were not statistically different between the 2 arms. 24 patients were treated with AZA monotherapy and 23 with AZA+entinostat. The median number of administered cycles was 4 and was significantly higher in patients treated with AZA monotherapy (6 cycles vs.3 cycles, p=0.008). 8 patients in the combination arm and 1 patient in the AZA monotherapy arm died of infection or hemorrhage before cycle 3. In an intent to treat analysis, overall response rates (CR, PR, or trilineage Hematologic improvement) were 11/24 (46%) in AZA monotherapy (95% CI 26 – 67%) and 4/23 (17%) in the combination arm (95% CI 5 – 39%, p=0.06 comparing the two arms). Median overall survival in the two arms were 12.8 months and 5.7 months (p=0.008). Conclusions In this group of very high risk patients with therapy-related myeloid neoplasms, the use of the novel 50 * 10 schedule of azacitidine monotherapy appears effective, with response rates comparable to those for patients with de novo MDS/AML treated on the same protocol (74 pts, 40% with unfavorable cytogenetics, ORR=32%, median OS=18 months). Because there are no prospective data examining the approved dose schedule of AZA (75 mg/m2/day * 7 days), it is not clear if this surprisingly high response rate derives from the current extended schedule of lower dose AZA, or would be true with standard dose AZA as well. This high response may enable many of these patients to proceed to allogeneic stem cell transplant. Entinostat combined with azacitidine at the dose and schedule applied in E1905 does not appear to be effective and tolerable as compared to azacitidine alone. Disclosures: Prebet: CELGENE: Honoraria. Off Label Use: Use of azacitidine in acute myeloid leukemia. Gore:CELGENE: Equity Ownership, Research Funding.

Abstract This study evaluated the contributing roles of flow cytometric immunophenotyping of blood and bone marrow and immunohistochemical paraffin section staining of bone marrow biopsies in the staging of B-cell malignant lymphoma. Flow immunophenotyping was performed on a marrow specimen in 175 cases; a corresponding blood specimen was also immunophenotyped in 135 of these cases. Morphologic marrow involvement by lymphoma was found in 59 cases; flow immunophenotyping identified 54 cases with a monoclonal B-cell process: morphology-positive/flow-positive (n = 49), morphology-positive/flow-negative (n = 10), morphology-negative/flow-positive (n = 5), and morphology-negative/flow-negative (n = 111). The 10 morphology-positive/flow-negative cases included 5 follicular and 5 large-cell lymphomas with minimal marrow involvement. All 5 morphology-negative/flow-positive cases were from patients with large-cell lymphomas and bulky clinical disease. Because the blood contained the same B-cell clone in 2 of 2 morphology-negative/flow-positive cases studied, blood contamination of marrow may account for these findings. Blood flow cytometric immunophenotyping studies were positive in 32 cases; 30 had marrow involvement by morphology and were from patients with follicular, mantle cell, lymphoplasmacytic, small lymphocytic, or marginal zone lymphomas. From our results, we conclude that (1) bone marrow flow cytometric immunophenotyping is not a cost-effective replacement for good morphologic evaluation in lymphoma staging and that (2) a positive peripheral blood flow cytometric immunophenotyping study when performed in low-grade lymphomas correlates with marrow involvement.

Abstract Abstract 971 Unlike the case in acute myeloid leukemia, there is limited information on the prognostic impact of IDH mutations in myelodysplastic syndromes (MDS). In the current study of 277 patients with MDS, IDH mutations were detected in 34 (12%) cases: 26 IDH2 (all R140Q) and 8 IDH1 (six R132S and two R132C). Mutational frequency was 4% (2 of 56) in refractory anemia with ring sideroblasts (RARS), 12% (16 of 130) in refractory cytopenia with multilineage dysplasia, 14% (2 of 14) in MDS-unclassifiable, 14% (6 of 42) in refractory anemia with excess blasts (RAEB)-1, and 23% (8 of 35) in RAEB-2. Normal karyotype was noted in all but one IDH1-mutated cases and 13 IDH2-mutated cases. Multivariable analysis identified presence of mutant IDH1 (p=0.0004; HR 4.0, 95% CI 1.9–8.8), revised International Prognostic Scoring System (IPSS-R) risk category (p<0.0001), and red cell transfusion need (p=0.002) as independent predictors of inferior survival (Figure 1). In a similar multivariable analysis, mutant IDH1 was the only variable associated with shortened leukemia-free survival (p=0.001; HR 7.0, 95% CI 2.3–20.8). The presence of IDH2 R140Q did not affect overall (p=0.54) or leukemia-free (p=0.81) survival (Figure 2). The current study suggests a powerful adverse prognostic effect for mutant IDH1 in MDS. Disclosures: No relevant conflicts of interest to declare.

This study evaluated the contributing roles of flow cytometric immunophenotyping of blood and bone marrow and immunohistochemical paraffin section staining of bone marrow biopsies in the staging of B-cell malignant lymphoma. Flow immunophenotyping was performed on a marrow specimen in 175 cases; a corresponding blood specimen was also immunophenotyped in 135 of these cases. Morphologic marrow involvement by lymphoma was found in 59 cases; flow immunophenotyping identified 54 cases with a monoclonal B-cell process: morphology-positive/flow-positive (n = 49), morphology-positive/flow-negative (n = 10), morphology-negative/flow-positive (n = 5), and morphology-negative/flow-negative (n = 111). The 10 morphology-positive/flow-negative cases included 5 follicular and 5 large-cell lymphomas with minimal marrow involvement. All 5 morphology-negative/flow-positive cases were from patients with large-cell lymphomas and bulky clinical disease. Because the blood contained the same B-cell clone in 2 of 2 morphology-negative/flow-positive cases studied, blood contamination of marrow may account for these findings. Blood flow cytometric immunophenotyping studies were positive in 32 cases; 30 had marrow involvement by morphology and were from patients with follicular, mantle cell, lymphoplasmacytic, small lymphocytic, or marginal zone lymphomas. From our results, we conclude that (1) bone marrow flow cytometric immunophenotyping is not a cost-effective replacement for good morphologic evaluation in lymphoma staging and that (2) a positive peripheral blood flow cytometric immunophenotyping study when performed in low-grade lymphomas correlates with marrow involvement.

Abstract Abstract 851 Clinical studies have demonstrated that acute myeloid leukemia (AML) is heterogeneous with respect to presentation and to clinical outcome, and many studies have shown that cytogenetics can be used to improve prognostication. More recently, it has been shown that FLT3, NPM1, and CEBPA mutations can be used to further risk stratify AML patients. Although recent studies have identified novel, recurrent somatic mutations in AML in genes including TET2, ASXL1, IDH1, IDH2, and PHF6, their prognostic value has not yet been evaluated among patients treated on a large phase III clinical trial. Here we report full-length DNA resequencing of FLT3, NPM1, CEBPA, H/K/NRAS, KIT, WT1, TET2, ASXL1, IDH1/2, TP53, RUNX1, PTEN, and PHF6 in pre-treatment genomic DNA from 398 patients with de novo AML younger than 60 years of age enrolled in the ECOG E1900 protocol. We could identify a clonal alteration, defined as a somatic mutation or cytogenetic abnormality, in 91.2% of all patients; 42% had 1 somatic alteration, 36.4% had 2 alterations, 11.3% had 3 alterations and 1.5% had 4 or more somatic alterations. Mutational Analysis: We identified somatic mutations in FLT3 (37% total; 30% ITD, 7% TKD), NPM1 (14%), CEBPA (10%), TET2 (10%), NRAS (10%), WT1 (10%), KIT (9%), IDH2 (8%), IDH1 (6%), RUNX1 (6%), ASXL1 (4%), PHF6 (3%), KRAS (2.5%), TP53 (2%), and PTEN (1.5%) (Figure 1A). We then performed correlation analysis to determine the frequency of different mutational combinations in AML patients. In addition to previously identified mutational correlations (FLT3 and NPM1, KIT and core binding factor leukemia), we found that FLT3 and ASXL1 mutations were mutually exclusive in this large cohort (p =0.0008). In addition, we found that IDH1/IDH2 mutations were mutually exclusive of both TET2 (p=0.02), and WT1 (p=0.01) mutations consistent with overlapping roles in AML pathogenesis (Figure 1B). Integration of mutational data with response data and outcome: Mutations in ASXL1 (CR rate 33.3% versus 66.5% for ASXL1-WT patients; p= 0.009) were enriched in patients who did not respond to induction chemotherapy. We found that mutations in FLT3 (p=0.0005), ASXL1 (p=0.005; Figure 1C), and PHF6 (p=0.02) were associated with reduced OS. Notably, the adverse effects of ASXL1 and PHF6 mutations on outcome were restricted to patients treated with standard dose daunorubicin (p<0.01 for each mutational cohort); ASXL1 and PHF6 mutational status did not affect outcome in patients treated with high-dose daunorubicin, demonstrating that increased intensity induction chemotherapy can improve outcomes in genetically defined poor risk AML subsets. We also found that mutations in CEBPA (p= 0.04) and in IDH2 (p=0.003) were associated with improved OS; the favorable impact of IDH2 mutations on outcome was exclusive to patients with IDH2 R140Q mutations (Figure 1D). Within the subset of patients with cytogenetically defined intermediate risk AML, we found, as expected, that FLT3-ITD mutations were associated with reduced OS and CEBPA mutations were associated with improved OS. Importantly, we found that IDH2 R140Q mutations were associated with improved OS (p=0.003) in patients with intermediate risk AML regardless of FLT3 mutational status. In contrast, TET2 mutations (P=0.0002) and PHF6 (p<0.0001) were associated with reduced OS in intermediate risk, FLT3-WT, AML. Summary: These data provide important clinical implications of genetic alterations in AML and provides insight into the multistep pathogenesis of adult AML. We identified novel mutations that impact response to induction chemotherapy and predict overall outcome, including ASXL1, PHF6, TET2 and IDH2, suggesting these mutations can be used to improve AML risk stratification and therapeutic decisions in AML patients 18–60 years of age. Most importantly, we identify TET2, IDH1/2, and WT1 mutations as mutually exclusive somatic alterations that form a novel mutational complementation group that contributes to AML pathogenesis. Figure 1. A) Circos diagram depicting relative frequency and pairwise co-occurrence of mutations in de novo AML patients enrolled in the ECOG protocol E1900. B) Circos diagram showing mutational events in IDH1/2, TET2, and WT1 mutant AML patient. C) Overall survival in AML patients with and without ASXL1 mutations (p=0.005). D) Overall survival in AML patients with and without IDH2 R172 and R140 mutations (p=0.003). Figure 1. A) Circos diagram depicting relative frequency and pairwise co-occurrence of mutations in de novo AML patients enrolled in the ECOG protocol E1900. B) Circos diagram showing mutational events in IDH1/2, TET2, and WT1 mutant AML patient. C) Overall survival in AML patients with and without ASXL1 mutations (p=0.005). D) Overall survival in AML patients with and without IDH2 R172 and R140 mutations (p=0.003). Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 3803 Background: Ring sideroblasts (RS) represent abnormal mitochondrial iron deposits that are commonly present in myelodysplastic syndromes (MDS). The presence of ≥15% RS, by definition (World Health Organization-WHO) is necessary for a diagnosis of a MDS-RS; with refractory anemia with ring sideroblasts (RARS) being a specific morphologic category. RS can also be seen with other morphologic categories such as; refractory cytopenias with multilineage dysplasia (RCMD), MDS-unclassifiable (MDS-U) and refractory anemia with excess blasts (RAEB-1/2). Amongst these categories, RARS is generally believed to have the best survival rate with the lowest risk of leukemic transformation and this has been attributed to the absence of associated dysplasia in more than one lineage. However, it has not been systematically shown whether or not the exact percentage of RS provides additional prognostic information in the context of an accurate morphologic categorization and risk stratification by karyotype or the revised IPSS (IPSS-R). Methods: 200 patients with primary MDS without excess blasts and ≥1% RS were seen at the Mayo Clinic from 1997 through 2007. All patients underwent bone marrow (BM) examination and cytogenetic evaluation at diagnosis and the pathology slides, including iron stains, were centrally re-reviewed to accurately quantify bone marrow (BM) RS percentage and to confirm WHO morphologic categories. Molecular profiling included analysis for IDH1, IDH2, JAK2 and MPL mutations. For the purposes of this study patients were divided into 4 categories based on the RS percentage; <5%, 5–14%, 15–50% and >50%. In addition, each patient was assigned IPSS and IPSS-R prognostic scores at diagnosis and risk stratified by karyotype according to the IPSS-R cytogenetic risk categories. Cox proportional regression method was used for multivariable analysis. Results: Of the overall 200 study patients, 140 (70%) were male and median age was 71 years (range, 17–90 years). At presentation, 34 (17%) patients were red cell transfusion-dependent. There were 56 (28%) patients with <5% RS (RCMD-52, MDS-U-14), 32 (16%) with 5–14% RS (RCMD-29, MDS-U-3), 79 (39%) with 15–50% RS (RARS-43, RCMD-29, MDS-U-2) and 33 (16%) with >50% RS (RARS-13, RCMD-17, MDS-U-3). Three patients (2%) were IDH1 mutant (RARS-1, RCMD-2), 17 (8%) IDH2 mutant (RARS-1, RCMD-14, MDS-U-2), 5 JAK2 V617F (3%) mutant (RARS-2, RCMD-3) and one patient with RCMD had the MPL W515L mutation. At a median follow-up of 33 months, 156 (73%) deaths and 24 (12%) leukemic transformations were documented. Median survivals were 63 months for MDS with >50% RS, 43 months for MDS with 15–50% RS, 35 months for MDS with 5–14% RS, and 14 months for MDS with <5% RS (p=0.005). In univariate analysis, additional risk factors included decreased hemoglobin, decreased platelet count, increased circulating blasts, WHO morphologic categories, red cell transfusion need, IPSS, IPSS-R and cytogenetic risk categories per IPSS-R. On a multivariable analysis only the IPSS-R prognostic score (p<0.0001) and the WHO morphologic categories (p=0.02 for RARS) retained significance. Univariate analysis disclosed significantly inferior leukemia-free survival (LFS) in patients with RCMD, thrombocytopenia, increased circulating blasts, and poor IPSS and IPSS-R prognostic scores. On multivariable analysis once again only the IPSS-R prognostic scores (p=0.02) and WHO morphologic categories (p=0.02) retained their significance. In other words, RS percentage, independent of WHO classification, as a continuous or categorical variable (i.e.: <5%, 5–14%, 15–50% & >50%) did not affect either overall survival or LFS. Conclusions: In MDS without excess blasts, once an accurate WHO morphologic categorization is made based on the presence or absence of multi-lineage dysplasia, there is no additional prognostic value for quantifying bone marrow ring sideroblasts. WHO classification and IPSS-R prognostic scores remain the most important factors in assessing patients with MDS. Disclosures: No relevant conflicts of interest to declare.

Abstract Introduction Inflammatory bowel disease (IBD) has a significant effect on patients’ overall quality of life (QoL). We hypothesized that an Electronic Health Record (EHR) patient portal (EPIC’s Mychart) can be utilized to improve QoL in IBD patients and increase vaccine uptake. Methods Patients were randomized to receive specific disease (INT) information and to a control arm (CTRL) that received periodic non-IBD related messages. Disease severity was assessed using the Harvey-Bradshaw index, and Simple Clinical Colitis Activity index. QoL was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Secondary outcome measures included overall satisfaction with the portal and influenza and pneumococcal vaccine uptake. Results One hundred twenty-seven patients were randomized: At baseline the CTRL group had a statistically significant higher QoL (Median SIBDQ 53.7) compared with the INT group (median SIBDQ 49.3), P = 0.04. At 6 months, the INT group had a trend towards a significantly greater increase in QoL (median SIBDQ 58) when compared with the CTRL group (median SIBDQ 57.5), P = 0.06. At 6 months more frequent portal use showed a significantly lower median SIBDQ (median 53) compared with patients with less frequent portal use (median 59), P = 0.038. At 6 months 88% of patients felt that the MyChart portal was useful with respect to IBD management. Patients had high rates of portal utilization with one-third of patients logging on weekly, and one-third logging on monthly. With respect to vaccine uptake, both influenza and pneumococcal pneumonia had higher rates of vaccine uptake. Conclusions Patients showed a trend towards improved QoL after receiving disease-specific information through our EHR portal. A significant increase in vaccine uptake was also seen. Frequent automated messages sent via an EHR portal can improve patient’s overall QoL. Larger studies will be needed to determine if automated portal reminders have a significant association with improved QoL, and furthermore to determine if there is any impact on disease activity.

Abstract Background Distinguishing Clostridioides difficile infection from colonization is challenging in patients with Inflammatory Bowel Disease (IBD). Cycle threshold (Ct), the cutoff for PCR positivity, has been investigated in non-IBD patients. Methods Patients with positive C. difficile PCR (25 IBD, 51 non-IBD) were identified retrospectively. Fifteen-day outcomes were assessed. Results Ct correlated with diarrheal days in non-IBD (P = 0.048), but not IBD patients (P = 0.769). IBD patients had shorter LOS and less severe infection, but more diarrheal days (P &lt; 0.05). Conclusions IBD patients had a milder course but Ct results were not significant. Larger studies are needed to clarify utility of Ct in IBD.

Abstract Abstract 4013 Background: In recent years, azacytidine (AZA) has become the standard of treatment for high risk myelodysplasia (MDS). The approved schedule of AZA uses a 75mg/m2/d s.c. regimen for 7 days based on the CALGB-9221 (Silverman, JCO 2002) and the AZA-001 studies (Fenaux, Lancet Oncol 2009). The clinical response rates after AZA have been extensively presented but there is only limited data on the rates of cytogenetic response (CyR). Based on the review of the literature, there are no specific cytogenetic data published on prospective trials. Methods: We based our analysis on a randomized phase 2 study from the US Leukemia Intergroup (E1905 study, NCT00313586) testing 10 days of AZA (50mg/m2/d s.c.) vs 10 days of AZA+ the histone deacetylase inhibitor entinostat (4 mg/m2/d PO days 3 and day 10). MDS, CMML, and AML with myelodysplasia-related changes were included. This analysis includes all patients with cytogenetic abnormalities (at baseline or acquired following treatment) with available cytogenetic follow-up (cycle 6). Of 150 patients, 70 demonstrated baseline cytogenetic abnormalities. To date, forty patients (27 MDS and 13 AML) were evaluable for both time points. Karyotypes were performed at local laboratories, and reviewed centrally (RPK and GH). Cytogenetic response was assessed using IWG 2000 (Cheson et al, Blood 2000) criteria. Results: The clinical response rate (CR+PR+ trilineage HI) according to IPSS cytogenetic risk stratification were of 20%, 33%, and 35% for favorable, intermediate and poor cytogenetic risk groups respectively (p=NS). Patients with Chr 7 abnormalities (i.e. -7 or -7q, n=18) had a response rate of 28% including 17% CR. Of patients with complete cytogenetic data, the rate of overall CyR was 52% (n=21): 22% (n=9) complete CyR, 30% (n=12) partial CyR. This represents a complete CyR of 13% and a partial CyR of 23% as a proportion of all treated patients with initial cytogenetic abnormalities (including those who did not receive six cycles of therapy). To date, confirmatory FISH analyses were available for 4 patients with CyR (2 CCyR and 2 PCyR). All four had complete clearance of their cytogenetic clone. Among the cytogenetic responders, 15 had MDS and 6 had AML (p=NS). CyR did not differ between the two treatment arms. CyR and clinical response were highly correlated (p<0.001): all patients with complete CyR and 7/10 partial CyR had a clinical CR. Only 3 patients (1 CCyR and 2 PCyR) had a CyR without associated clinical response. Among 8 patients with cytogenetic progression, 3 pts showed increased frequency of a known aberration and 5 showed new or additional aberration including 2 cases involving Chr7. 65 AZA-treated patients from AZA001 had comparable cytogenetic results available. Only 3 patients experienced complete CyR 4.6% with 33.8% partial CyR (n=22). In contrast, the reported rate of clinical response was similar in the two studies. Complete CyR were more frequent in the E1905 10 days AZA schedule compared to the 7 days AZA schedule (p=0.007). There was no difference in overall CyR between the two studies. Conclusions: Both the standard AZA schedule and the 10 day schedule administered on E1905 lead to high rates of cytogenetic response. The novel schedule explored in E1905 demonstrated a particularly high rate of complete CyR (22%) with complete clearance of abnormal clone by FISH in 4 tested patients. Further prospective comparison of different AZA schedules will be needed to confirm this higher rate of complete CyR and determine its clinical significance. Disclosures: Beach: Celgene: Employment. Gore:Celgene: Consultancy, Research Funding, stock options; Syndax: Consultancy.

Abstract Background: SL-401 is a novel targeted therapy directed to the interleukin-3 receptor (CD123), a target overexpressed by many hematologic malignancies. SL-401 is currently being advanced through clinical trials in patients with a variety of CD123+ malignancies including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML) in remission with high relapse risk, and multiple myeloma. CD123 has been shown to be expressed on myeloproliferative neoplasm (MPN) cells as well as microenvironmental immune cells, namely plasmacytoid dendritic cells (pDCs), in the bone marrows of some patients with MPN including chronic myelomonocytic leukemia (CMML). Microenvironmental pDCs have been implicated in promoting plasma cell disorders and preliminary data suggest that pDCs could play a related role in some myeloid neoplasms. Accordingly, a therapy directed at both CD123-expressing myeloid cells and neighboring CD123-expressing pDCs could provide therapeutic benefit. SL-401 is being evaluated in patients with advanced, high-risk MPN, including systemic mastocytosis (SM), myelofibrosis (MF), primary eosinophilic disorders (PED), and CMML. Preliminary results are reported here. Methods & Results: This multicenter, single-arm Phase 2 trial of patients with advanced, high risk MPN includes a lead-in (stage 1) and expansion (stage 2). In stage 1, patients receive SL-401 as a daily IV infusion at 7, 9, 12 ug/kg/day, or higher for days 1-3 of a 21-28 day cycle in a 3x3 design. In stage 2, patients receive SL-401 at the dose determined in stage 1. Study objectives include characterization of the safety profile, including determination of the maximum tolerated or tested dose, and detection of preliminary efficacy signals including evaluation of tumor response and progression free survival by standard criteria. As of 7/20/16, 6 patients with MPN (MF, n=3; CMML-2, n=2; CMML-1, n=1) received SL-401 (7 ug/kg, n=3; 9 ug/kg, n=3). The median age was 66 years (range: 42-81 years). Patients treated at all doses received 1+ to 2+ cycles (ongoing) of SL-401. The most common treatment-related adverse events (AEs) were thrombocytopenia (2/6; 33%) and fatigue (2/6; 33%); the most common ≥ Grade 3 treatment-related AEs were thrombocytopenia (2/6; 33%) and anemia (1/6; 17%); there has been no DLT. Efficacy assessments are ongoing. Patients are currently enrolling in the 12 ug/kg/day cohort. Conclusions: Initial dosing of SL-401 appears to be well-tolerated in patients with MPN and CMML, with no unexpected AEs observed. Given CD123 expression on myeloid neoplastic cells as well as microenvironmental immune cells (namely, pDCs), SL-401 may offer a novel, targeted therapeutic approach in patients with high-risk MPN and CMML of unmet medical need. Enrollment continues in stage 1 of this ongoing Phase 2 trial and updated safety and efficacy data will be presented. Clinical trial information: NCT02268253. Disclosures Gupta: Novartis: Consultancy, Honoraria, Research Funding; Incyte Corporation: Consultancy, Research Funding. Carraway:Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Baxalta: Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees. Schiller:Incyte Corporation: Research Funding. Talpaz:Incyte Corporation: Other: Travel expense reimbursement, Research Funding; Ariad: Other: Expense reimbursement, travel accomodation expenses, Research Funding; Novartis: Research Funding; Pfizer: Consultancy, Other: travel accomodation expenses, Research Funding. McCloskey:Novartis: Speakers Bureau; Incyte: Consultancy; Ariad: Consultancy, Speakers Bureau; Amgen: Speakers Bureau. Lee:Alexion Pharmaceuticals: Consultancy; Amgen: Consultancy; Baxalta: Consultancy; Boehringer Ingelheim: Consultancy; Pfizer Inc: Consultancy. Yacoub:Alexion: Honoraria; Seattle Genetics: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau. Ali:Incyte Corporation: Research Funding. Chen:Stemline Therapeutics, Inc.: Employment, Equity Ownership. Shemesh:Stemline Therapeutics: Employment, Equity Ownership. Brooks:Stemline Therapeutics, Inc.: Employment, Equity Ownership, Patents & Royalties.