Austrian Azacitidine Registry Research Articles

Cox Proportional Hazards Deep Neural Network Identifies Peripheral Blood Complete Remission (PB-CR) to be at Least Equivalent to Morphologic CR in Predicting Outcomes of Patients Treated with Azacitidine - a Prospective Cohort Study By the AGMT

Background Myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) are multiclonal diseases demonstrating considerable biologic, phenotypic, genetic, and clinical overlap. In recognition of this continuum, these diseases are often treated similarly. Achievement of complete remission (CR)/CR-incomplete (CRi) is deemed the major outcome associated with improved overall survival (OS), and is often used as primary endpoint in clinical AML trials, whereas red blood cell transfusion independence is often the endpoint used in MDS trials. Expert opinions questioning these endpoints are cumulating [Sekeres M, Leukemia 2019, 570; Kim N, BJH 2021, 1137; Chandhok N, Leuk Lymphoma 2022, 1], as are reports indicating that achievement of CR/CRi may not be necessary for prolonged OS in patients treated with azacitidine [Pleyer L, Annals Hematol 2014, 1825; Schuh AC, ASH 2015, P575; Pleyer L, ASH 2015, P3752; Pleyer L, ASH 2019, P3387]. All response criteria for MDS, CMML and AML require bone marrow evaluations (BME), which are only performed in ~50% of patients outside of clinical trials [Dinmohamed A, Leuk Res 2015, 177; Pleyer L, ASH 2019, P3387], indicating the real-world need for internationally accepted response endpoints that do not necessitate repeated BME. We thus introduced peripheral blood CR (PB-CR), defined as Hb ≥11.0 g/dL, PLT ≥100 and <450 G/L, ANC ≥1.0 G/L, WBC ≥1.5 and <10.0 G/L, monocytes ≤1.0 G/LPB blasts=0%, no growth factors, no transfusions). In 1441 patients treated with azacitidine, multivariate survival modelling adjusted for 17 baseline covariates, indicated that PB-CR is at least as good a predictor of OS as CR [Pleyer L, ASH 2019, P3387]. Aims To compare the predictive value of CR or CR/CRi versus PB-CR. Methods Data from 1441 patients receiving 13971 cycles of azacitidine included in the Austrian Azacitidine Registry NCT01595295 was used for expanded analyses. The endpoints OS, time to next treatment (TTNT) and time on treatment (TOT) were defined as described previously [Pleyer L, Lancet Haematology 2021, e135]. Only data from patients who had a BME during treatment, and for whom all 17 baseline variables remaining in the final Cox model [Pleyer L, ASH 2019, P3387] were available, were analyzed (n=624). DeepSurv, a Cox proportional hazards model parametrized by a deep neural network [Katzman J, BMC Med Res Meth 2018, 24], was used to assess the predictive value of CR, CR/CRi and PB-CR. The network architecture is depicted in Fig 1. To assess whether CR or CR/CRi has greater predictive value than PB-CR, model performance was evaluated on randomly corrupted (i.e. destroyed) data. Either CR, CR/CRi or PB-CR responses were randomly permutated 1000 times, thus removing the information content from the respective variable and allowing investigation of the resulting drop in model performance using the concordance index (C-index). The average validation C-index for each response type of the corrupted datasets was generated with 5-fold cross-validation (Fig 2), stratified by sex, age </≥75 years and diagnosis. Validation C-index pairs for each of the 1000 permutations were compared by Wilcoxon signed-rank test. Bonferroni-correction for multile testing was performed. Results Random permutations of the PB-CR response resulted in signficantly higher performance loss than random permutations of the response types CR or CR/CRi, indicating that PB-CR has significantly more information content than either CR or CR/CRi. The C-indices with "intact PB-CR and permutated CR (or CR/CRi) were significantly higher than for "intact CR (or CR/CRi) and permutated PB-CR", with p<0·0001 for the endpoints TOT, TTNT and OS (Fig 3). Results remained consistent irrespective of the choice of inner network architectures. Conclusions In the largest cohort of azacitidine treated patients reported to date, survival modelling with a neural Cox regression revealed a higher information content for PB-CR as compared to either CR or CR/CRi for all time-to-event endpoints analyzed. Presence of PB-CR can thus identify patients with adequate response to non-intensive therapies without repeated BM assessments. Incorporation of PB-CR as secondary endpoint in clinical trials would be ideal to confirm these results. We aim to analyse whether these findings can be recapitulated in MDS, CMML and AML patients receiving other treatments and welcome collaborations. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The EQ-5D-5L Predicts Treatment Outcomes and Provides Added Value to the R-IPSS in Patients with MDS, CMML or AML Treated within the Austrian Azacitidine Registry - a Prospective Cohort Study By the AGMT Study Group

The EQ-5D-5L Predicts Treatment Outcomes and Provides Added Value to the R-IPSS in Patients with MDS, CMML or AML Treated within the Austrian Azacitidine Registry - a Prospective Cohort Study By the AGMT Study Group

Peripheral Blood Complete Remission Provides Added Value to the Classical Definition of Morphologic Complete Remission - a Prospective Cohort Study of 1441 Patients with MDS, CMML and AML Treated within the Austrian Azacitidine Registry

Peripheral Blood Complete Remission Provides Added Value to the Classical Definition of Morphologic Complete Remission - a Prospective Cohort Study of 1441 Patients with MDS, CMML and AML Treated within the Austrian Azacitidine Registry

Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group.

We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine (“AML-001” cohort; n = 214) with AAR patients meeting the same inclusion criteria (“AAR (001-like)” cohort; n = 95). The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (p = 0.616) for “AML-001” versus “AAR (001-like)” cohorts, respectively. Secondly, we pooled data from both cohorts (n = 309) and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6) months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (n = 95) versus all AAR patients with World Health Organization (WHO)-defined AML (“AAR (WHO-AML)” cohort; n = 193). Within the registry population, median OS for AAR patients meeting trial inclusion criteria versus all WHO-AML patients was 10.8 versus 11.8 months (p = 0.599), respectively. We thus tested and confirmed the efficacy of azacitidine as a front-line agent in patients with AML, >30% BM blasts and WBC ≤ 15 G/L in a routine clinical practice setting. We further show that the efficacy of azacitidine does not appear to be limited to AML patients who meet stringent clinical trial inclusion criteria, but instead appears efficacious as front-line treatment in all patients with WHO-AML.

Azacitidine in Acute Myeloid Leukemia with >30% Bone Marrow Blasts and

BackgroundIn the Phase III trial (AML-001; NCT01074047) that assessed azacitidine (AZA) vs conventional care regimens (CCR; intensive chemotherapy, low-dose cytarabine or best supportive care as preselected by the treating physician) in older patients (≥65 years) with newly diagnosed acute myeloid leukemia (AML) and >30% bone marrow (BM) blasts, AZA was associated with a clinically meaningful improvement in overall survival (OS) vs CCR.1Patient registry data, if performed with adequate quality control, can complement and be of additional value to data generated in clinical trials. The Austrian Azacitidine Registry (AAR; NCT01595295) was initiated to gain a comprehensive view of the use, safety and efficacy of AZA in patients with AML in a 'real world' clinical practice setting.2,3 No formal exclusion criteria existed, as the aim was to include all AML patients treated with AZA, irrespective of age, comorbidities, and/or previous lines of treatment.2,3Aims and methodsThe aim of this analysis was to assess the efficacy and safety of 1st -line AZA in patients with AML who were included in the AAR and who fulfilled the BM blast percentage and white blood cell (WBC) count entry criteria of the AML-001 trial (BM blasts >30% and WBC <15G/L). Outcomes of the subgroups of patients with poor-risk cytogenetics and with AML and myelodysplasia-related changes (AML-MRC) who received 1st -line AZA were also evaluated.ResultsA total of 95 patients were identified that fulfilled the BM blast percentage and WBC count entry criteria of the AML-001 trial (data cut-off June 19 2015). Apart from a higher proportion of AML-MRC and a lower proportion of AML-not otherwise specified (AML-NOS) within the AAR, baseline characteristics were comparable to those observed in AML-001 (i.e. age, BM blast percentage, gender, therapy-related AML, prior myelodysplastic syndrome (MDS), Eastern Cooperative Oncology Group Performance Status (ECOG PS), cytogenetic risk, transfusion dependence, hemoglobin level, WBC count, absolute neutrophil count, and platelet (PLT) count; Figure 1). Patient status at data cut-off, reasons for AZA discontinuation and treatment characteristics were also similar: median number of AZA cycles was 5 (1-51) and 6 (1-28) for the AAR and AML-001 trial, respectively (Figure 1). Patient outcome in terms of overall response according to International Working Group criteria4 (31.5 vs 29.0%), red blood cell (42.1 vs 38.5%) and PLT transfusion independence (34.5 vs 40.6%) did not differ significantly between the AAR and the AML-001 trial. Furthermore, median OS was highly concordant between the AAR and AML-001 overall (10.8 vs 10.4 months; Figure 2A) as well as for various patient subgroups: 12.2 vs 12.7 months for patients with AML-MRC (Figure 2B); 14.6 vs 14.1 months for patients with normal cytogenetics; 13.1 vs 13.0 months for patients with intermediate-risk cytogenetics; and 7.2 vs 6.4 months for patients with high-risk cytogenetics (Figure 2C). After 1 year, 47.4% of patients were still alive in the AAR cohort compared with 46.5% in the AML-001 trial (p=0.924). Event-free survival was 5.5 (range: 0-35.3) vs 6.7 (range: 5-8.8) months in the AAR and AML-001 trial, respectively. The 30-day (8.4 vs 6.6%; p=0.642) and 60-day (15.5 vs 16.2%; p=0.903) mortality rates were comparable. The incidence of febrile neutropenia (24.2 vs 28.0%) and Grade 3-4 treatment-emergent (TE) neutropenia were similar between the AAR and AML-001; however, higher rates of TE thrombocytopenia (47.4 vs 15.7%; p=0.023) and anemia (31.6 vs 26.3%; p<0.001) were observed in the AAR.ConclusionThese data confirm the safety and efficacy of AZA in a patient-population for whom this drug has not yet been approved, i.e. AML with more than 30% BM blasts and without leukocytosis. These data therefore complement prospective clinical trial data and support the role of well-designed and in-depth clinical registries.

Azacitidine in Acute Myeloid Leukemia: Comparison of Patients with AML-MRF Vs AML-NOS Enrolled in the Austrian Azacitidine Registry

Azacitidine in Acute Myeloid Leukemia: Comparison of Patients with AML-MRF Vs AML-NOS Enrolled in the Austrian Azacitidine Registry

Azacitidine in Patients with Relapsed/Refractory Acute Myeloid Leukemia : Retrospective Analysis of the Austrian Azacitidine Registry

Azacitidine in Patients with Relapsed/Refractory Acute Myeloid Leukemia : Retrospective Analysis of the Austrian Azacitidine Registry

Azacitidine in Patients with Treatment-Related Acute Myeloid Leukemia: Retrospective Analysis of the Austrian Azacitidine Registry

Azacitidine in Patients with Treatment-Related Acute Myeloid Leukemia: Retrospective Analysis of the Austrian Azacitidine Registry

Azacitidine in patients with WHO-defined AML – Results of 155 patients from the Austrian Azacitidine Registry of the AGMT-Study Group

ObjectiveThe Austrian Azacitidine Registry is a multi-center database (ClinicalTrials.gov: NCT01595295). The nature and intent of the registry was to gain a comprehensive view of the use, safety and efficacy of the drug in a broad range of AML-patients treated in real-life scenarios.Patients and methodsThe sole inclusion criteria were the diagnosis of WHO-AML and treatment with at least one dose of azacitidine. No formal exclusion criteria existed. A total of 155 AML-patients who were mostly unfit/ineligible for intensive chemotherapy, or had progressed despite conventional treatment, were included. True ITT-analyses and exploratory analyses regarding the potential prognostic value of baseline-variables/performance-/comorbidity-/risk-scores on overall survival (OS), were performed.ResultsIn this cohort of 155 pretreated (60%), and/or comorbid (87%), elderly (45% ≥75 years) AML-patients, azacitidine was well tolerated and efficacious, with an overall response rate (CR, mCR, PR, HI) of 45% in the total cohort (ITT) and 65% in patients evaluable according to IWG-criteria, respectively. Pre-treatment with conventional chemotherapy (P = .113), age ≤/>80 years (P = .853), number of comorbidities (P = .476), and bone marrow (BM) blast count (P = .663) did not influence OS. In multivariate analysis hematologic improvement alone (without the requirement of concomitant bone marrow blast reduction), although currently not regarded as a standard form of response assessment in AML, was sufficient to confer OS benefit (18.9 vs. 6.0 months; P = .0015). Further deepening of response after first response was associated with improved OS (24.7 vs. 13.7 months; P < .001).ConclusionsIn this large cohort of AML-patients treated with azacitidine, age >80 years, number of comorbidities and/or BM-blasts >30% did not adversely impact OS.

Activity of Azacitidine in 26 Unselected, Consecutive CMML Patients Included in the Austrian Azacitidine Registry (AAR) of the AGMT-Study Group

Abstract 1715Twelve participating centers in Austria included 257 unselected, consecutive patients with MDS/CMML or AML, who received azacitidine (AZA) between 02/2007 and 07/2011, in the nationwide Austrian Azacitidine Registry (AAR) of the AGMT-study group. Approval by the national Ethics Committee was obtained. The AAR includes 26 patients with CMML (10 with CMML-1, 16 with CMML-2) and is currently the 2nd largest report on CMML patients treated with AZA, the largest comprising 36 evaluable patients (Costa R. et al., Cancer, June 2011, pp2690). Myeloproliferative CMML (MP-CMML), defined as WBC>13.000/μl at diagnosis, was present in 16/26 patients, whereas 10/26 had myelodysplastic CMML (MD-CMML). Thus, the AAR includes patients for whom AZA is currently not approved by the FDA/EMEA.The AAR includes a high proportion of very old CMML patients (31% 75–79a, 15% >80a). Median age was 75a for both males (n=15) and females (n=11). Patients with various levels of PS were included (ECOG-0 (n=6), ECOG-1 (n=14), ECOG-2 (n=8) and ECOG-3 (n=4)). CMML-patients of the AAR suffered from renal insufficiency (n=8), mild liver disease (n=8), coronary artery disease (n=5), diabetes mellitus (n=5), a prior/concomitant solid tumor (n=3), COPD (n=2) and/or venous thromboembolic disease (n=1), respectively. There was no relevant difference in RBC transfusion dependence (TD) for MP-CMML vs. MD-CMML. However, PLT-TD at diagnosis was lower for MP-CMML (23%) than for MD-CMML (67%). In the 19 patients in whom pretreatment cytogenetics were performed, 15, 4 and 0 could be grouped into IPSS good, intermediate and poor risk categories, respectively. Only 57% of all included CMML-patients were treatment-naïve, whereas the rest were pretreated with ICT (10%), ESA (14%), intensive chemotherapy (21%) and other substances (17%) (mainly hydroxyurea and anagrelide) (numbers add up to more than 100% as several patients were pretreated with more than 1 agent). Thus, this registry more accurately reflects a real-life treatment scenario, than most clinical trials that have strict inclusion/exclusion criteria.Most AZA-cycles were applied s.c. (98%), whereas 2% were applied i.v. Median and mean number of AZA-cycles was 5.5 and 9 (SD 10.61; range 1–43), respectively. The FDA-approved d1-7 schedule was used in 62% of all AZA cycles, whereas the non-approved alternative schedules d1-5, 5-2-2 and ‘others' were applied in 21%, 12% and 6% of all cycles, respectively. Concerning the number of patients however, 20/26 predominantly received the d1-7 schedule. The FDA-approved target dose (75mg/m2 over 7 days) was achieved in 52% of all cycles and in 17/26 of patients, respectively.Reasons for termination of treatment with AZA were death (33%), disease progression (22%), transformation to AML (11%), no response (6%), toxicity (6%) and other reasons (22%).Any kind of HI was noted in 12/26 (46%) of patients. When looking at each lineage separately, 8/26 had HI-ery, 7/26 HI-PLT and 9/26 HI-neutrophils. 6/14 patients who were RBC-TD and 3/7 patients who were PLT-TD prior to AZA-treatment achieved transfusion independence (TI). In patients, in whom (repetitive) bone marrow aspirations/biopsies were performed for response evaluation (n= 12), the following best marrow responses were observed: CR in 4/12 (33%), marrow CR 1/12 (8%), PR in 2/12 (16%), SD in 4/12 (33%) and primary PD in 1/12 (8%). The OR rate observed prior to 07/2011 was 44% (CR + marrow CR + PR + HI). At the time of writing, 9 patients had received <=2 cycles. When limiting response analysis to patients who received >2 AZA cycles, which is required for achievement of hematologic response by the IWG-criteria, ORR was 66%. These are amongst the highest response rates observed for CMML to date.The median OS was 12.7 months (95%CI 6.9; 19.4). Median OS for patients demonstrating HI was significantly higher than for those who did not (19.4 vs. 5.6 months, p<0.0001). Detailed OS analyses and statistical analyses of various factors known or thought to influence prognosis are currently being analyzed, including MP-CMML vs. MD-CMML, CMML-1 vs. CMML-2, comparison of IPSS cytogenetic risk groups, as well as treatment-naïve vs. pretreated patients.In conclusion, in this population of partly pretreated, comorbid, very old patients with CMML, AZA was well tolerated and yielded substantial clinical and hematological benefit. Disclosures:Pleyer:Celgene: Research Funding. Off Label Use: Azacitidine for treatment of CMML including CMML-1 with transfusion-dependence and MP-CMML. Melchardt:AOP Orphan Pharmaceuticals AG: Research Funding. Egle:AOP Orphan Pharmaceuticals AG: Research Funding. Fridrik:Cephalon: Research Funding. Greil:AOP Orphan Pharmaceuticals AG: Research Funding.

Azacitidine Is Feasible and Safe in Patients with MDS and Co-Existing Plasma Cell Dysplasias (PCD) - Report on 9 Patients From the Austrian Azacitidine Registry (AAR)

Abstract 5056Azacitidine (AZA) has been approved for the treatment of higher-risk MDS and therefore marks a cornerstone in the development of hypomethylating agents. Recent clinical trials raise questions regarding optimal sequencing and also about combining hypomethylating agents with other classes of drugs targeting epigenetic processes. It has been postulated that unspecific demethylation of promotors may lead to the activation of oncogenes, and therefore result in an elevated rate of secondary malignancies.We report on 9 patients from the Austrian Azacitidine Registry (AAR) with co-excisting plasma cell dyscrasias (PCD) receiving treatment with AZA for MDS. Six male and 3 female patients had a median age of 73 years at time of diagnosis of MDS and 73 years at time of diagnosis of PCD. They were diagnosed with Waldenstrom macroglobulinemia (WMG) (n=3), multiple myeloma (n=2) and MGUS (IgG (n=2), IgM (n=1), IgA (n=1)). All PCD were diagnosed either before or at least at the same time as MDS. None occurred after diagnosis of MDS or after treatment initiation with AZA. However, one patient with multiple myeloma likely had treatment–related MDS due to prior treatment with MPT (melphalan, prednisone, thalidomide).At the time of writing, the mean number of AZA cycles given was 9 (range 1–27). Two patients were concomitantly treated with Rituximab (R) whilst on AZA treatment. Importantly, no additional toxicities occurred and there seemed to be no negative interaction between Rituximab and AZA. In all patients treated with AZA for MDS, M-gradient remained stable, and in some cases significant improvement was noted. One patient even achieved complete remission of WMG following AZA/R treatment (data will be shown; Weiss L et al, J Clin Oncol. 2011 Jul 25 [Epub ahead of print]). Importantly, no progression of PCD was seen in any of the 9 patients treated with AZA, and PCD did not contribute to death in any of these patients.In conclusion, AZA treatment of MDS in patients with co-existing PCD seems safe, combination with Rituximab seems feasible, no aggravation of PCD was seen and remarkably, one patient with WMG achieved CR following AZA/R. Disclosures:Pleyer:Celgene: Research Funding. Egle:AOP Orphan Pharmaceuticals AG: Research Funding. Greil:AOP Orphan Pharmaceuticals AG: Research Funding.

Report on Response and Overall Survival of 128 Unselected, Consecutive AML Patients From the Austrian Azacitidine Registry (AAR) of the AGMT-Study Group

Abstract 4266Twelve participating centers in Austria included 257 unselected, consecutive patients with MDS, CMML or AML, who received azacitidine (AZA) between 02/2007 and 07/2011, in the nationwide Austrian Azacitidine Registry (AAR) of the AGMT-study group. This registry was approved by the national Ethics Committee and includes 128 patients with AML of all FAB-subtypes, as well as de novo AML (39%), t-AML, MDS-AML and post-CMPD-AML.This registry comprises a large number of patients with >30% bone marrow blasts (83/128) (currently off-label indication for AZA), as well as myeloproliferative AML (35/128), as defined by presence of >10.000 WBC/μ l at diagnosis. The AAR includes a high proportion of very old AML patients (median age 73a, 20% 75–79a, 24% >80a). Although the PS was generally low (22% ECOG-0, 47% ECOG-1), AML patients suffered from coronary artery disease (n=29), renal insufficiency (n=26), diabetes mellitus (n=21), a prior/concomitant solid tumor (n=17), COPD (n=14) and/or mild liver disease (n=13), respectively. Only 40% of all AML-patients included were treatment-naïve, whereas the rest was pretreated with G-CSF (12%), ESA (9%), ICT (3%) revlimid or thalidomide (6%), other agents (11%) and/or intensive chemotherapy (47%), respectively. Thus, this registry more accurately reflects a real-life treatment scenario, than most clinical trials that have strict inclusion/exclusion criteria.In the 93 patients in whom pre-AZA cytogenetics were performed, 56.9%, 25.8% and 17.2% could be grouped into IPSS good, intermediate and poor risk categories, respectively. Of these, 43 patients had MDS-specific cytogenetic aberrations (5q-, +8, -7, -7q, -Y and -20q). Most AZA-cycles were applied s.c. (89%), whereas 11% were applied i.v. Median and mean number of AZA-cycles was 4.0 and 5.6 (range 1–24), respectively. 60% of patients predominantly received the FDA-approved d1-7 schedule, whereas the non-approved alternative schedules 5-2-2, d1-5 and ‘others' were most often given in 17%, 16% and 7% of patients, respectively. The FDA-approved target dose (75mg/m2 over 7 days) was achieved in 58% of all cycles and in 61% of patients, respectively.Longitudinal repetitive analysis of serum GOT, GPT, bilirubin and creatinine over up to 24 cycles shows no relevant variation or worsening tendency of these parameters during treatment with AZA, including patients with reduced baseline renal and/or hepatic function.Reasons for termination of treatment were death for any reason (26%), disease progression or relapse (27%), no response (6%), toxicity (7%), recurrent infectious complications (2%) and other reasons (23%). Adverse events will be presented in detail (number, grade, duration, hospitalization rate, effects on AZA (dose reductions/treatment pause/termination)).Any kind of hematologic improvement (HI) was noted in 38% of patients. When looking at each lineage separately, 21/128 had HI-ery, 23/128 HI-PLT and 24/128 HI-neutrophils. 35/85 patients who were RBC-TD and 19/55 patients who were PLT-TD prior to AZA-treatment achieved transfusion independence (TI). In patients, in whom (repetitive) bone marrow analyses were performed for response evaluation (n= 56), the following best marrow responses were observed: CR (19.6%), marrow CR (7.1%), PR (33.9%), SD (30.4%) and primary PD (8.9%). At the time of writing, 35 patients had received ≤2 cycles. This number largely accounts for the patients in whom no bone marrow response evaluation was performed. The OR rate observed prior to 07/2011 was 38% (CR + marrow CR + PR + HI). When limiting response analysis to patients who received ≥2 AZA cycles, which is required for achievement of hematologic response by the IWG-criteria, ORR was 57%.The median OS was 9.5mo (95%CI 8.15–10.9). In univariate analyses, ECOG >=2 (p=.0026), circulating blasts (9.3 vs. 24.8mo; p=.0014), IPSS poor risk cytogenetics (p=.0037) and failure to achieve any HI (8.6 vs. 22.4mo; p=.0001), significantly negatively impacted OS. Prior treatment with G-CSF and/or ESA, age >80a, WBC >10G/l, BM blasts >30%, LDH >225U/l, number of cytopenic lineages as well as RBC-TD and/or PLT-TD at baseline, did not significantly impact OS (p>0.05) (detailed statistics will be presented).In conclusion, in this population of partly heavily pretreated very old patients with AML, AZA was well tolerated and yielded substantial clinical and hematological benefit, irrelevant of baseline BM blast or PB WBC count. Disclosures:Pleyer:Celgene: Research Funding. Off Label Use: Azacitidine for treatment of AML including patients with >30% bone marrow blasts. Egle:AOP Orphan Pharmaceuticals AG: Research Funding. Fridrik:Cephalon: Research Funding. Greil:AOP Orphan Pharmaceuticals AG: Research Funding.

101 Age- and comorbidity-specific evaluation of azacitidine treatment, response and overall survival in 184 patients in the Austrian Azacitidine Registry

101 Age- and comorbidity-specific evaluation of azacitidine treatment, response and overall survival in 184 patients in the Austrian Azacitidine Registry

100 Overall survival data of patients with MDS, AML and CMML from the Austrian Azacitidine Registry of 184 consecutive patients

100 Overall survival data of patients with MDS, AML and CMML from the Austrian Azacitidine Registry of 184 consecutive patients