ALBERT

Description: Background: The cytogenetic hallmark of chronic myeloid leukemia (CML) is a translocation, t(9;22)(q34;q11), resulting in the Philadelphia (Ph) or derivative 22 chromosome. Cytogenetic studies indicate that 90-95% of cases have the Ph chromosome or recognized variant (Ph+ CML), with the remaining 5-10% having a normal or near normal karyotype despite the presence of the BCR-ABL fusion (Ph-negative, BCR-ABL-positive CML). Tyrosine kinase inhibitors (TKIs) have been approved for the treatment of patients with Ph+ CML. The effect of TKIs in patients with Ph- CML has not been described in detail. Objective: ENEST1st (Evaluating Nilotinib Efficacy and Safety in clinical Trials as First-Line Treatment) sub-group analysis was planned to explore the effect of nilotinib in patients with Ph- CML. Patients and Methods: ENEST1st (NCT01061177) is a phase 3b, multicenter, open-label study of nilotinib 300 mg twice daily (BID) in adults with newly diagnosed BCR-ABL+ CML-CP. Patients with confirmed Ph- CML-CP were included in the sub-analysis. Primary endpoint was rate of MR4 (defined as BCR-ABL ≤ 0.01% on the International Scale [BCR-ABLIS] or undetectable BCR-ABL in cDNA with ≥ 10,000 ABL transcripts) at 18 mo. Results: Of the 1089 patients included in ENEST1st study, 30 patients (2.7%) were Ph- (only one of those had a cytogenetic aberration [del9q34]), 983 patients (90.3%) were Ph+ and 76 (7.0%) patients had an unknown karyotype at baseline. Among these patients, 28 pts (2.7%) Ph- and 952 pts (90.5%) Ph + with b2a2 and/or b3a2 BCR-ABL transcripts and treated with imatinib for ≤ 3 mo were analyzed for molecular response (MR). Median age of patients with Ph- CML was 51.5 years (range, 21.0 to 75.0). EUTOS score was low in 86.7% and high in 6.7% of patients (6.7% missing). Sokal risk score was low, intermediate, and high in 33.3%, 30.0%, and 23.3% of patients, respectively (13.3% missing). In Ph+ CML patients, the median age was 53.0 years (range, 18.0 to 91.0). EUTOS score was low in 82.0% and high in 9.2% of pts (8.9% missing). Sokal risk score was low, intermediate, and high in 34.8%, 37.2%, and 18.1% of pts, respectively (9.9% missing). The MR4 rate at 18 mo in Ph- population was 39.3% (95% CI, 21.2% - 57.4%). The cumulative incidence of MR4 by18 mo was60.7% (95% CI, 42.6% - 78.8%). Rates of cumulative MMR (BCR-ABLIS ≤0.1%) and MR4.5 (BCR-ABLIS ≤0.0032%) by 18 mo were 85.7% (95% CI, 72.8% - 98.7%) and 46.4% (95% CI, 28.0% - 64.9%), respectively. For the Ph+ CML population, the MR4 rate at 18 mo was 38.1% (95% CI, 35.0% - 41.2%). The cumulative incidence of MR4 by 18 mo was48.1% (95% CI, 44.9% - 51.3%). Rates of cumulative MMR (BCR-ABLIS ≤0.1%) and MR4.5 (BCR-ABLIS ≤0.0032%) by 18 mo were 76.8% (95% CI, 74.1% - 79.5%) and 31.4% (95% CI, 28.5% - 34.4%), respectively. Rates of MMR, MR4, and MR4.5 at 18 and 24 mo among Ph- population and the Ph+ CML population are summarized in the Table. The 3-month BCR-ABL level has been shown to be predictive of MR in the Ph+ CML population. Among Ph- population not pretreated with imatinib (n = 14), 85.7% achieved BCR-ABLIS ≤ 1%, no patients had BCR-ABLIS 〉 1% to ≤ 10% and 〉 10% at 3 mo. Two patients did not have the assessment at 3 mo. Among patients with Ph+ CML not pretreated with imatinib (n = 802), 70.0% , 17.0%, and 2.7% of patients achieved BCR-ABLIS ≤ 1% , 〉 1% to ≤ 10%, and 〉10% respectively. Eighty-five patients did not have the assessment at 3 mo. Most common AEs experienced by the Ph- population were hypophosphatemia (25%), rash (18%), pruritus (14%), nasopharyngitis (14%), alanine aminotransferase increase (14%), and blood bilirubin increase (14%). In the Ph+ population, the list of most common AEs includes rash (22%), pruritus (17%), headache (16%), and fatigue (14%). Conclusions: The MR rates observed in Ph- CML subgroup are similar to the rates observed in Ph+ CML patients. These results indicate that nilotinib is active in this previously unexplored population as well and larger studies should be conducted to confirm the results. The safety results observed in Ph-CML patients are similar to the ones observed in the Ph+ CML pts. aCML patients with typical b2a2 and/or b3a2 BCR-ABL transcripts and ≤3 mo of prior imatinib Figure 1. Figure 1. Disclosures Hochhaus: ARIAD: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Mahon:Novartis: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Coriu:BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Honoraria, Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees. Ossenkoppele:Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; ARIAD: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Cross:Ariad: Consultancy, Honoraria, Research Funding; Qiagen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Müller:Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding. Rea:Pfizer: Honoraria; Ariad: Honoraria; BMS: Honoraria; Novartis: Honoraria. Steegmann:Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Ariad: Honoraria, Research Funding. Castagnetti:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria. Hellmann:Novartis: Research Funding; BMS: Research Funding. Rosti:Novartis: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria, Research Funding, Speakers Bureau. Gattermann:Novartis: Honoraria, Research Funding. Gutierrez:BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; PFIZER: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Tubazio:Novartis: Employment. Pellegrino:Novartis: Employment. Dezzani:Novartis: Employment. Giles:Novartis: Consultancy, Honoraria, Research Funding.

Description: Background: Bone marrow (BM) examination is essential in the staging of diffuse large B-cell lymphoma (DLBCL). The assessment of BM involvement includes both histology (gold-standard) and flow cytometry (FC), but few studies have compared BM biopsy (BMB) histologic findings with results of FC analysis of BM aspirate. Discordance between both techniques generates debate about the staging and the prognostic significance in these cases. Methods: We performed a retrospective single-center analysis of patients with DLBCL, not otherwise specified (NOS) diagnosed during a 4-year period (2014-2017). Patients were divided in three groups according to BM findings of BMB and FC at diagnosis. Standard FC was performed by 4-color flow panel until 2016 and by 8-color FC since then. We described main characteristics of each group at diagnosis and analyzed survival outcomes. We applied means of descriptive statistics and Pearson's chi-squared test, and analyzed survival outcomes according to Kaplan-Meier, using Cox regression for comparisons. Results: We analyzed 59 cases, which were divided in three groups: 40 cases (67.8%) presented both negative histology and FC (BMB-/FC-), 10 (16.9%) showed BM involvement using both histology and FC (BMB+/FC+) and 9 cases (15.3%) presented discordant results, all of them with negative histology and positive FC (BMB-/FC+). Clinical and biological characteristics of each group at diagnosis are presented in Table 1. Median infiltration by FC analysis of the BMB-/FC+ group was 0.8% (0.1-2.9) and 3/9 patients presented discordant immunophenotype of lymphoma cells between BM and node biopsy. If we considered BM infiltration as positive in all BMB-/FC+ cases, 4/9 (6.8% of all patients) would be upstaged. First-line treatment was homogeneous in all patients. With a median observation time of 18 months, progression-free survival (PFS) after 2 years was 67%, 22% and 22% with BMB-/FC-, BMB-/FC+ and BMB+/FC+, respectively (Figure 1A), with a multivariate hazard ratio (HR) of 1.9 (95% CI 1.2-2.9, p=0.004) and an univariate HR for FC+ (BMB-/FC+ and BMB+/FC+) vs FC- (BMB-/FC-) of 3.3 (95% CI 1.5-7.3, p=0.003). Two-year overall survival (OS) was 68%, 41% and 33% with BMB-/FC-, BMB-/FC+ and BMB+/FC+, respectively (Figure 1B); multivariate HR was 1.6 (95% CI 1.1-2.6, p=0.042) and univariate HR for FC+ vs FC- was 2.5 (95% CI 1.1-5.9, p=0.035). We found no significant difference between BMB-/FC+ and BMB+/FC+ in survival outcomes. Conclusions: In our series, the group with discordant BM infiltration (BMB-/FC+) presented worsen survival outcomes than BMB-/FC-. Such results should be validated in prospective studies because published series are retrospective and not focused specifically on DLBCL. BM infiltration detected by FC analysis but not by BMB could be considered as extranodal involvement at DLBCL NOS diagnosis. Disclosures García Gutiérrez: Novartis: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Incyte: Consultancy, Research Funding, Speakers Bureau.

Description: Introduction The simultaneous detection of autoantibodies and alloantibodies to red blood cells (RBC) following allogeneic transfusion is poorly understood. The incidence of autoimmune hemolysis in these patients is not well established (Young et al., Transfusion 2004; 44: 67-72). Methods Patients with a positive antibody screen, an identified alloantibody and a positive direct antiglobulin test (DAT) were selected from our hospital Blood Bank database from January 2002 to June 2013. Sex, age, main clinical diagnosis, transfusion history, alloantibody and autoantibody specificity and hemolysis parameters were analysed retrospectively in those patients with simultaneous first detection of auto and alloantibodies. In our Blood Bank, all patients to be transfused underwent a three-cell antibody screen by gel technology (Ortho Clinical Diagnosis). If the screen was positive, two microcolumn panels with eleven cells (DianaGel) and an autocontrol were performed in Liss-Coombs and with papain-treated erythrocytes for antibody identification. Test-tube testing at different temperatures with Reagent RBC (Makropanel) and a polyethyleneglycol (PEG) antiglobulin technique were carried out to confirm antibody specificity when deemed appropriate. Polyspecific and monospecific (anti-IgG and C3d) DAT (Menarini reagents) and a 6% albumin negative control were performed in all patients presenting a positive autocontrol. Acid glycine elution (Gamma ELU-KIT II) was the method of choice to prepare the eluates. Adsorption techniques were used in some cases to remove autoantibodies. Results A total of 2915 patients formed alloantibodies; 4.5% (n=132) presented both auto- and alloantibodies. The temporal relationship between the antibodies detected had the following distribution: 96.2% (n=127) simultaneous auto- and alloantibody, 2.3% alloantibody identification and on subsequent studies autoantibody and 1.5% had autoantibody previous to alloimmunization. The following results will refer to the group with simultaneous detection of auto and alloantibodies. In the selected group, 55% had a complete register of previous RBC transfusion with a median of 8.5 transfusions lifelong (range: 2 to 81) and a median of 38.5 days (range: 4 to 270 days) between last negative and first positive antibody screen. The ratio male to female was 1:1 and the median age was 67 years-old (range: 20 to 91 years-old). The most common diagnosis in these patients were: solid neoplasia (21.3%), oncohematologic disease (13.4%; mielodysplastic syndromes were included in this subgroup), chronic hepatopathy (15%; of which 58% are HVC-related), cardiovascular disease (9.5%), traumatism (7%), pregnancy (3.2%) and autoimmune disease (3.1%). The most frequent alloantibodies identified were: anti-E (39.3%) 〉 anti-C (28.3%) 〉 anti-K (24.5%). Most autoantibodies had no apparent specificity (67%), those that did have a specific pattern were related to Rh antigens (anti-e 7%; anti-c 1.5%; anti-D 1.5%), and the remainder 23% were crioagglutinins. A total of 16 patients (12.5%) had concomitant hemolysis at the time of antibody detection of which 43.7% (n=7) had an active cancer (57% due to oncohematologic disease), 25% (n=4) HCV hepatopathy and 12.5% autoimmune hepatitis (n=2). Conclusion Patients with de novo alloimmunization showed concomitant antierythrocytic autoantibodies in 4.5% of our population. Most cases appear to be related to previous RBC transfusion and medical conditions affecting normal immunological functioning. However, hemolysis was only found in 12.5% of these patients at the time of antibody detection and all of them had diseases with a known associated risk of developing autoimmune anemia. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: Transformation to secondary myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PV) and essential thrombocythemia (ET), the two more indolent Ph-negative myeloproliferative neoplasms (MPN). Once transformed, survival is remarkably shorted. Chronic inflammation plays a critical role in the progression of MPN, driving clonal expansion toward end stage disease. Importantly, MPN are characterized by the production of inflammatory cytokines, by both malignant and non-malignant clone. Inflammation and cancer share a common pathway, i.e. NF-κB. Interestingly, miR-146a regulates TLR/NF-κB pathway through the inhibition of its targets, IRAK1 and TRAF6, decreasing the production of cytokines. Based on: i) miR-146a-/- mice develop an MF-like phenotype with aging; and ii) miR-146a polymorphism (miRSNPs) rs2431697, influences its expression levels (50% decrease in TT individuals); we hypothesized that lower miR-146a-5p levels associated to this miRSNPs may result in high risk to develop MF. Objective: To evaluate the association of rs2431697 with MF transformation and to study the molecular mechanisms beyond this association. Methods: We genotyped rs2431697 in 938 patients (312 MF, 299 PV, and 327 ET) recruited from 13 tertiary Spanish institutions belonging to GEMFIN and 600 controls. The levels of miR-146a and IRAK1 were evaluated by qRT-PCR in total blood RNA of homozygous patients (TT=30, CC=25) with PV or ET and in healthy subjects (TT=7, CC=7). In miR-146a-/- mice, 2 and 9 months old, we evaluated spleen size and cellularity: degree of fibrosis in bone marrow (H&E and silver staining); and STAT3 and pSTAT3 in granulocytic lysates by western blot. Results: Association analysis, taken controls as reference, showed that TT genotype (associated in the literature with low levels of mir-146a) is associated to MF with an OR of 1.36 (1.01-1.82, p=0.04). Among MF patients, the subgroup with the greatest differences was the one of secondary MF (OR = 1.47, CI: 0.98-2.20) (Table 1 a,b). Next, we compared the genetic frequencies of rs2431697 SNPs between the secondary MF patients and the population in risk. Confirming our hypothesis, we observed an enrichment of TT genotype in the post-PV/TE MF group (n=132) compared to the PV+TE group (n=626) (OR=1.51; p

Description: Introduction: Tyrosine kinase inhibitor (TKI) discontinuation is being investigated in pts with CML-CP with sustained DMR (defined here as MR4.5 or BCR-ABL1 ≤ 0.0032% on the International Scale [IS]), with the goal of treatment-free remission (TFR). Successful TFR has been reported previously for pts enrolled in DASFREE (CA180-406/NCT01850004), which showed that 48% of CML-CP pts with DMR for ≥ 1 year were able to stop dasatinib and maintain major molecular response (MMR) 12 months after discontinuation. Here we present updated results from pts followed for a minimum of 18 months, in order to understand the durability of TFR beyond 12 months. Methods: DASFREE is a phase 2, open-label, single-arm study in adult pts with CML-CP on dasatinib for ≥ 2 years as 1st-line or subsequent therapy. Eligible pts had dasatinib-induced DMR (MR4.5) confirmed at a local lab for ≥ 1 year prior to enrollment, with a 1-log reduction in BCR-ABL1 from baseline within 3-6.5 months of starting dasatinib. MR4.5 was confirmed at a central lab twice within 3 months prior to dasatinib discontinuation (screening phase). BCR-ABL1 was monitored centrally after discontinuation every month in the 1st year, then every 3 months. Pts resumed dasatinib at their previous dose if MMR was lost. The primary endpoint is the rate of MMR 12 months after dasatinib discontinuation. Secondary endpoints include BCR-ABL1 kinetics, molecular relapse-free survival (MRFS; no loss of MMR), relapse-free survival (RFS; no loss of MMR, complete cytogenetic response, or complete hematologic response, or progression to accelerated/blast phase [AP/BP] CML), rate of transformation to AP/BP, progression-free survival, and overall survival. Exploratory analyses include frequency of adverse events (AEs) after discontinuation and during dasatinib treatment, and MMR after reinitiating dasatinib. Results: In total, 84 pts enrolled between February 2014 and June 2016 discontinued dasatinib; all had ≥ 18 months of follow-up after discontinuation at the time of this analysis. Pt characteristics were previously reported (the majority [64%] had low Sokal scores; no pt had prior interferon; 37 pts were on 1st-line dasatinib, 47 on subsequent lines of dasatinib). At 18 months after discontinuation, the RFS rate was 48% (95% CI 37-58) in all pts (Figure), 54% (95% CI 38, 70) in 1st-line pts, and 42% (95% CI 28, 57) in pts who received subsequent-line therapy. With longer follow-up, 1 additional pt lost MMR at 18 months following discontinuation. Of the 45 pts who lost MMR and restarted treatment, 44 regained MMR (1 pt discontinued after only 1 molecular assessment) in a median of 2 months (range 1-4) and 42 regained MR4.5 in a median of 3 months (range 2-18). Analyses of baseline pt characteristics revealed that for the 40 pts who did not lose MMR after discontinuation, 15 (37.5%) were able to maintain MR4.5. Additionally, the median time in prior MR4.5 was 28 months (range 13-116) for all pts, and was similar for 1st-line pts who maintained (27 months [range 13-56]) or lost MMR (27 months [range 15-68]) at 12 months. With longer follow-up, AEs (any cause) identified were consistent with previous reports and were found to be similar on and off treatment: 8 (10%) pts off treatment and 8 (18%) pts on treatment experienced grade 3/4 AEs of any cause after restarting dasatinib (4.4% were drug related). No transformation events or deaths occurred. Of the 13 reported withdrawal events occurring in 8 (9.5%) pts, 10 were resolved (5 off treatment, 5 resolved after restarting treatment due to loss of MMR) after a median of 5 months (range 1-12) after onset. One pt discontinued after restarting dasatinib due to malignancy unrelated to treatment. In addition to efficacy and safety data, multivariate analyses evaluating prognostic factors for MMR will be presented. Conclusions: Additional follow-up of pts enrolled in DASFREE revealed that TFR remained durable at 18 months after discontinuing dasatinib. AEs reported here were consistent with the known safety profile of dasatinib, and withdrawal was well tolerated. Collectively, this trial, the largest dasatinib discontinuation trial to date, continues to support the feasibility and practicality of TFR in pts with CML-CP in DMR treated with dasatinib in the 1st line and beyond. Figure. Figure. Disclosures Shah: ARIAD: Research Funding; Bristol-Myers Squibb: Research Funding. García Gutiérrez:Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Incyte: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau. Larson:Bristol-Myers Squibb: Consultancy; Takeda: Speakers Bureau. Saussele:Bristol-Myers Squibb: Honoraria, Research Funding; Incyte: Honoraria; Novartis: Honoraria, Research Funding; Pfizer: Honoraria. Rea:Incyte: Honoraria; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria. Mahon:Bristol-Myers Squibb: Speakers Bureau; Incyte: Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Speakers Bureau. Levy:Takeda (Millennium Pharmaceuticals, Inc.): Consultancy. Gómez-Casares:Novartis: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Incyte: Speakers Bureau. Pane:Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Incyte: Consultancy. Nicolini:Incyte: Consultancy, Honoraria, Speakers Bureau; Sun Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria, Speakers Bureau. Mauro:Pfizer: Consultancy; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy; Novartis: Consultancy, Research Funding. Sy:Bristol-Myers Squibb: Employment. Martin Regueira:Bristol-Myers Squibb: Employment, Equity Ownership. Lipton:ARIAD: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding.

Description: BACKGROUND The phase 3 REACH2 trial (NCT02913261; N = 309) was the first successful randomized study in SR aGVHD, demonstrating that RUX, a JAK1/2 inhibitor, was superior to BAT. At day 28, RUX pts had a significantly higher overall response rate (ORR) than BAT pts (62.3% vs 39.4%; P 〈 .001). RUX also led to a higher durable ORR at day 56 (39.6% vs 21.9%; P 〈 .001) and showed clinically meaningful treatment benefits across pt subgroups of baseline characteristics; failure-free survival was longer with RUX (5.0 vs 1.0 month; HR, 0.46; 95% CI, 0.35 to 0.60) (Zeiser R, et al. NEJM. 2020). The safety profile of RUX was as expected in pts with SR aGVHD, with cytopenias being the most common adverse events (AEs). To further define the safety profile of RUX in SR aGVHD, we report additional safety data up to day 28. METHODS Pts ≥ 12 years old with grade II-IV aGVHD following allogeneic hematopoietic cell transplant (alloHCT) who were refractory to steroids were randomized 1:1 to RUX (starting dose, 10 mg bid) or investigator-selected BAT and stratified by aGVHD grade. Crossover to RUX was allowed in BAT pts who had not responded by day 28 or lost response thereafter. Safety was assessed during the randomized treatment period by monitoring the frequency, duration, and severity of AEs, including AEs of special interest (AESI; ie, cytopenias, infections, bleeding events, other). AEs were assessed according to the Common Terminology Criteria for Adverse Events v4.03. Infections were also assessed by investigators using an infection-specific grading system predictive of mortality that was developed for and validated in alloHCT recipients (Cordonnier C, et al. Transplantation. 2006). Infections were classified by type (viral, bacterial, fungal, unknown, other) and severity (grades 1 to 3). We report AEs up to day 28, when exposure to RUX and BAT was similar. RESULTS A total of 302 pts (RUX, n = 152; BAT, n = 150) received ≥ 1 dose of study drug and were included in this analysis. Most pts experienced ≥ 1 AE up to day 28, with similar rates observed between RUX (96.1% [grade ≥ 3, 78.3%]) and BAT (94.7% [grade ≥ 3, 79.3%]). The most common AEs (all grades [grade ≥ 3]) in RUX vs BAT pts were thrombocytopenia (32.9% [27.0%] vs 18.7% [16.0%]), anemia (30.3% [22.4%] vs 28.0% [18.7%]), and cytomegalovirus (CMV) infection/reactivation (25.7% [7.2%] vs 20.7% [8.0%]). However, AEs led to low rates of discontinuation (RUX, 11.2%; BAT, 4.0%), primarily due to anemia (2.0% vs 0.7%), thrombocytopenia (2.0% vs 0%), and pancytopenia (1.3% vs 0%). Serious AEs occurred in 37.5% of RUX pts and 34.0% of BAT pts. The most commonly reported serious AEs were sepsis (RUX, 5.3%; BAT, 2.0%), diarrhea (3.3%; 0.7%), and CMV infection/reactivation (2.6%; 3.3%), with sepsis leading to death in 3 RUX pts (2.0%) and 2 BAT pts (1.3%). Among AESI, the most common events were infections excluding tuberculosis (RUX, 61.2% [grade ≥ 3, 32.2%] vs BAT, 58.7% [grade ≥ 3, 37.3%]) and thrombocytopenia (50.0% [41.4%] vs 32.7% [29.3%]). The risk of developing an AESI was similar between RUX and BAT pts, except for the risk of thrombocytopenia, which was higher in pts receiving RUX (Figure). A total of 15 deaths in the RUX arm (9.9%) and 21 in the BAT arm (14.0%) occurred up to day 28. The main cause of death in both arms was aGVHD, with higher rates seen in the BAT arm (11.3% vs 5.9% in the RUX arm). When assessed using the grading system developed by Cordonnier et al, infections were reported in 61.2% (grade 3, 22.4%) of RUX pts and 55.3% (grade 3, 18.7%) of BAT pts. Among pts with infection, the median time to first occurrence of infection was 2.1 (range, 0-27.0) weeks with RUX vs 1.9 (range, 0-21.3) weeks with BAT. Main types of infections were viral (RUX, 42.8%; BAT, 33.3%), bacterial (29.6%; 32.7%), and fungal (8.6%; 4.7%). The most common viral infections in RUX vs BAT pts were CMV (grade 3, 4.6% vs 3.3%) and Epstein-Barr virus (no grade 3); the most common bacterial infections were urinary tract (no grade 3), device-related (no grade 3), and sepsis (grade 3, 2.6% vs 2.0%); and the most common fungal infections were bronchopulmonary aspergillosis (grade 3, 2.0% vs 0%) and oral candidiasis (no grade 3). CONCLUSIONS The safety profile of RUX was consistent with what has been previously reported and what is expected in pts with SR aGVHD, including a higher risk of developing thrombocytopenia with RUX. Up to day 28, the risk of developing other AESI was similar between RUX and BAT. No new or unexpected safety findings were observed. Disclosures Von Bubnoff: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Clinical biomarker research, steering committee, Patents & Royalties: Research support, Research Funding; Astra Zeneca: Honoraria, Other: Lectures, Patents & Royalties: Astra Zeneca. Wagner:MSD: Membership on an entity's Board of Directors or advisory committees; Medac: Other: Travel grand; Shire: Other: Travel grand; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Forcade:JAZZ: Other: Travel grant for congress; NEOVII: Other: Travel grant for congress; Gilead: Speakers Bureau; Novartis: Other: Travel grant for congress; Sanofi: Other: Travel grant for congress. Civriz Bozdag:Novartis: Research Funding. Ayuk:Neovii: Research Funding; Therakos/Mallinckrodt: Honoraria, Research Funding; Kite/Gilead: Honoraria; Celgene: Consultancy, Honoraria; Novartis: Honoraria. Yoon:Amgen: Consultancy, Honoraria; Kyowahako Kirin: Research Funding; Novartis: Consultancy, Honoraria; Janssen: Consultancy; F. Hoffmann-La Roche: Other: All authors received support for third-party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland., Research Funding; YuhanPharma: Research Funding. García Gutiérrez:Novartis Pharma AG: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding. Rubio:Medac: Consultancy; Gilead: Honoraria; MSD: Honoraria; Novartis: Honoraria; Neovii: Research Funding. Xu:Novartis: Current Employment. Morando:Novartis: Current Employment. Mahuzier:Novartis: Current Employment. Chandraiah:Novartis: Current Employment. Socié:Incyte: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Consultancy, Honoraria, Research Funding; Elsalys: Honoraria.

Description: Background: Data from the phase 2, single-arm ENESTfreedom study (NCT01784068) have demonstrated the feasibility of treatment-free remission (TFR) following front-line nilotinib (NIL) treatment, with substantial TFR rates being sustained over time among patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP). Results for long-term outcomes after a 5-year follow-up are presented here. The current subanalysis evaluated the efficacy and safety of TFR after upfront treatment with NIL in older (≥65 years [yrs] at study entry) vs younger (

Description: Sickle Cell Anemia (SCA) is highly prevalent in sub-Saharan Africa (SSA). In Uganda, approximately 20,000 children are born with SCA annually (Ndeezi G, 2016). Sickle brain vasculopathy causes both overt strokes and clinically "silent infarcts," affecting neurological and cognitive function (DeBaun MR, 2012). Incidence of strokes has markedly decreased through standardized preventative measures. Study objectives are to determine the age-related spectrum and burden of brain injury associated with SCA in Ugandan children, determine predisposing risk factors and build capacity to support interventions for stroke prevention. Here we present preliminary results. Methods: BRAIN SAFE is a cross-sectional study of a random sample of 250 children with SCA, ages 1-12 years, who receive care at the Mulago Hospital SCD clinic in Kampala.Potential participants were randomly selected from the clinic roster. Study exclusion criteria: hemoglobinopathy other than HbSS or HbS B0 thalassemia, age 〉12, acute illness, Hb 12, acute illness, severe anemia, recent transfusion or participation in another study. History and neurological exam : Overall, 7 of 233 had history consistent with a stroke, and an abnormal neurological exam, 5 had a history consistent with stroke but a normal neurological exam, 6 had abnormal neurological findings but no history of stroke (total abnormal 18/233, 7.7%). Psychometrics : To date, cognitive test data results have been performed on 80 children; 30 (37.5%) were impaired with varying severity. (Full reports to follow.) TCDs : A total of 224 non-imaging TCDs have been performed. Using standard criteria, 190 were normal, 4 abnormal (1.8%), and 30 conditional (13.4%). Repeat TCDs have been performed on 13 of those with non-normal reads and so far, 2 were abnormal, 6 conditional, 4 normal,1 had difficult windows. MRI/MRAs: A subset of 29 subjects were selected with more clinical and/or historical stroke pathology (N= 25, 86%) and have undergone MR imaging to date (see Table). Mean age was 7.1 years (range 3-12); male: 55%. Of 26 with clinical radiological reads, 16 / 26 (61.5%) were abnormal. To date, scans from 12 subjects have had SCD vascular reads: 2 had no vasculopathy; 10 were abnormal: 6 with infarcts and arterial stenoses, 3 with infarcts only, 1 with bilateral stenoses only. Conclusions: BRAIN SAFE, a Kampala-based cross-sectional study, has already enrolled and completed a large proportion of study procedures. Considerable brain pathology has been identified in all aspects tested, with high prevalence of abnormal history or physical findings, abnormal psychometrics, abnormal cerebral blood flow and/or brain MR imaging. Completion of enrollment and testing for the target sample will provide baseline data for longitudinal assessment and intervention. Building research capacity for faculty and trainees is ongoing. Acknowledgments: 1R21HD089791 (PIs: Idro, Green) and Latanya Bowman, RN, Augusta University Sickle Cell Center. Disclosures No relevant conflicts of interest to declare.