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In: Journal of Hematology & Oncology, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2016-12)

Type of Medium: Online Resource

ISSN: 1756-8722

URL: Article

DOI: 10.1186/s13045-016-0263-4

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2016

detail.hit.zdb_id: 2429631-4

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3742-3742

Abstract: Background Current response criteria for AML were established for and validated in younger patients (pts) fit for and treated with intensive chemotherapy (IC) in an era before hypomethylating agents (HMA) were available. According to these criteria: 1 Achievement of morphologic complete response (CR; defined as bone marrow blasts [BMB] 〈 5%, absolute neutrophil count 〉 1.0G/L, platelets ≥100G/L and red blood cell transfusion independence) is a prerequisite for cure, and is deemed the sole outcome associated with improved overall survival (OS)1 2 Pts without morphologic CR are considered non-responders1 3 Morphologic leukemia free state (MLFS; defined as 〈 5% BMB, irrespective of cytopenias) is considered inferior to CR 4 Hematologic improvement (HI) without BMB clearance is considered treatment failure1,2 However, evidence is accumulating that these definitions may not be applicable to older AML pts treated with HMA. For example, achievement of CR with HMA may not be necessary for clinical benefit and prolonged OS.3-5 We have previously shown that older AML pts achieving HI according to myelodysplastic syndrome (MDS) criteria6 have clinical benefit from extended azacitidine (AZA) treatment.3,4 In addition, treatment goals and modalities differ for HMA vs IC. Thus, the question arises whether current response criteria remain valid for older AML pts unfit for IC. Aims and methods To define new response criteria, including the 1st criteria for assessment of HI, for older AML pts unfit for IC with the intention of keeping them as simple to implement as possible. Human errors in response assessment according to these proposed criteria were excluded by the development of algorithms for automated computational calculation from data entered into the eCRF. We next assessed the supplementary value of HI in addition to BMB reduction, as well as the value of HI irrespective of BMB reduction, with regards to predicting treatment outcomes. Results In total, 193 AML pts receiving AZA 1st line were included in this analysis. Baseline and treatment characteristics were mostly comparable to those of AML pts included in a recent phase 3 clinical trial (Fig 1).7 Overall, 5 categories of HI and hematologic progression were defined, using: erythrocytes (E), platelets (P), neutrophils (N), peripheral blood blasts, and elevated white blood cells (Fig 2). We based our definitions on IWG 2006 MDS criteria and adapted these for the more aggressive disease biology and kinetics of AML, and treatment goals and modalities of HMA. Our data indicate that: 1 AML pts achieving HI (irrespective of BMB reduction) had significantly longer OS than those without HI (16.1 vs 6.0 mo, p 〈 0.001; Fig 3A) 2 OS was prolonged irrespective of the cell lineage in which HI occurred (17.1, 17.5 and 18.0 mo for pts with HI-N, HI-E or HI-P, respectively) 3 OS correlated with the number of cell lineages/types in which HI was achieved (6.0 vs 14.4 vs 19.7 mo [p 〈 0.001] for HI in 0 vs 1-2 vs 〉 2 lineages/types; Fig 3B) 4 Pts with MLFS did not have worse OS than pts with CR (Fig 3C) 5 Definition of response according to our proposed criteria resulted in clinically meaningful separation of 3 response types with significant differences in median OS: 23.0 (CR or MLFS) vs 13.5 (HI and not CR or MLFS) vs 4.4 mo (non-responders) (p 〈 0.001; Fig 3D) Conclusions While achievement of CR according to IWG 2003 criteria1 remains the primary goal for AML pts treated with IC, we guardedly introduce new response criteria for pts unfit for IC treated with non-curative treatment such as HMA. Applying these criteria to our large real world cohort, we show that pts achieving HI in the absence of BMB clearance (considered non-responders using current criteria)1, had a significant survival benefit from continued AZA treatment compared to pts with no HI. We conclude that these patients should be considered as responders and kept on treatment, and hypothesize that achievement of HI could be used as a surrogate parameter for response in pts unable or unwilling to undergo BM biopsy for response assessment. This proposal requires concerted validation efforts and we hope that our data stimulate cooperations. References 1 Cheson BD JCO 2003;21:4642 2 Lopez G Blood 2001;98:329;abs 1388 3 Pleyer L J Hematol Oncol 2013;6:32 4 Pleyer L Ann Hematol 2014;93:1825 5 Schuh AC Haematologica 2015;100:abs P575 6 Cheson BD Blood 2006;108:419 7 Dombret H Blood 2015;126:291 Disclosures Pleyer: AOP Orphan Pharmaceuticals: Honoraria; Novartis: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Off Label Use: Vidaza (azacitidine) is indicated for the treatment of adult AML patients who are not eligible for hematopoietic stem cell transplantation with 20-30% blasts and multi-lineage dysplasia, according to WHO classification. This cohort also includes AML patients with 〉 30% bone marrow blasts.. Burgstaller:Celgene: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; Mundipharma: Honoraria; AOP Orphan Pharmaceuticals: Honoraria, Research Funding. Girschikofsky:Pfizer: Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria. Sill:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Thaler:AOP Orphan: Research Funding. Halter:Medical University Innsbruck: Employment. Zebisch:Celgene: Honoraria. Pichler:Celgene: Honoraria. Pfeilstöcker:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Autzinger:Wilhelminenspital: Employment. Lang:Celgene: Consultancy. Geissler:Celgene: Membership on an entity's Board of Directors or advisory committees. Geissler:Klinikum Klagenfurt: Employment. Sperr:Celgene: Consultancy; Ariad: Consultancy. Hojas:LKH Fürstenfeld: Employment. Greil:Amgen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria; Astra-Zeneca: Honoraria; Cephalon: Consultancy, Honoraria, Research Funding; Celgene: Consultancy; Ratiopharm: Research Funding; GSK: Research Funding; Sanofi Aventis: Honoraria; Novartis: Honoraria; Janssen-Cilag: Honoraria; Genentech: Honoraria, Research Funding; Eisai: Honoraria; Mundipharma: Honoraria, Research Funding; Merck: Honoraria; Bristol-Myers-Squibb: Consultancy, Honoraria; AOP Orphan: Research Funding; Roche, Celgene: Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.3742.3742

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 2515-2515

Abstract: Background In 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.2,3 Aims and methods The 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. Results A 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. Conclusion These 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. References 1. Dombret H, et al. Blood 2015;126:291-9 2. Pleyer L, et al. J Hematol Oncol 2013;6:32 3. Pleyer L, et al. Ann Hematol 2014;93:1825-38 4. Cheson BD, et al. J Clin Oncol 2003;21:4642-9 Disclosures Pleyer: Celgene: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; AOP Orphan Pharmaceuticals: Honoraria. Off Label Use: Vidaza (azacitidine) is indicated for the treatment of adult AML patients who are not eligible for hematopoietic stem cell transplantation with 20-30% blasts and multi-lineage dysplasia, according to WHO classification. This cohort also includes AML patients with 〉 30% bone marrow blasts.. Burgstaller:Novartis: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; AOP Orphan Pharmaceuticals: Honoraria, Research Funding; Mundipharma: Honoraria. Girschikofsky:Mundipharma: Consultancy, Honoraria; Pfizer: Honoraria, Research Funding. Sill:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Thaler:AOP Orphan: Research Funding. Halter:Medical University Innsbruck: Employment. Zebisch:Celgene: Honoraria. Pichler:Celgene: Honoraria. Pfeilstöcker:Novartis: Consultancy, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Autzinger:Wilhelminenspital: Employment. Lang:Celgene: Consultancy. Geissler:Celgene: Membership on an entity's Board of Directors or advisory committees. Geissler:Klinikum Klagenfurt: Employment. Sperr:Ariad: Consultancy; Celgene: Consultancy. Hojas:LKH Fürstenfeld: Employment. Greil:Astra-Zeneca: Honoraria; Ratiopharm: Research Funding; GSK: Research Funding; Sanofi Aventis: Honoraria; Pfizer: Honoraria, Research Funding; Eisai: Honoraria; AOP Orphan: Research Funding; Novartis: Honoraria; Celgene: Consultancy; Merck: Honoraria; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; Genentech: Honoraria, Research Funding; Roche, Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Janssen-Cilag: Honoraria; Boehringer-Ingelheim: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.2515.2515

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3387-3387

Abstract: Background In myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) achievement of complete remission (CR) is a prerequisite for potential cure. In AML, CR/CR with incomplete recovery (CRi) is deemed the major outcome associated with improved overall survival (OS); patients (pts) without CR/CRi are considered non-responders, and hematologic improvement (HI) without (assessment of) bone marrow (BM) blast clearance is considered treatment (trt) failure. Achievement of CR may not be necessary for prolonged OS in pts treated with azacitidine (AZA) (Pleyer L, Annals Hematol 2014, 1825; Schuh AC, ASH 2015, P575). Outside of clinical trials, BM evaluations (BME) are only performed in ~50% of pts (Dinmohamed, Leuk Res 2015, 177) when either response or progression are obvious from peripheral blood (PB) values, or when pts are unable or unwilling to have BME. Aims To assess of the impact of response type on AZA trt outcomes in multivariate adjusted analyses (MVA). Methods 1441 pts included in the Austrian Azacitidine Registry were analyzed (NCT01595295). Data cut-off was 1 July 21. Marrow response was assessed for MDS/CMML and AML at each BME; HI was assessed on day 1 of each AZA cycle (Döhner H, Blood 2017, 424; Cheson BD, Blood 2006, 419; Pleyer L, ASH 2019, P3821); peripheral blood complete remission (PB-CR) was defined as hemoglobin ³11 g/dL, platelet count ≥100 G/L, neutrophil count ³1.0 G/L, white blood cell count & lt;15 G/L, PB blasts =0%, and no transfusions. Response types were calculated from electronic case report form data. To identify which response type achieved by which AZA cycle had the highest impact on time-to-event endpoints, likelihood ratios (LR) of the Cox-regression model for OS or time to next treatment (TTNT) were calculated using the respective response types as covariates. Baseline characteristics with univariate p & lt;0·10 (n=23) for association with OS were included in the multivariate regression. After stepwise selection n=17 variables remained and were used for MVA. Assign Data Management and Biostatistics GmbH performed statistical analyses with SAS® 9.4. Results In total, 521, 135, and 785 pts had MDS, CMML and AML. Median year of initial diagnosis was 2012, median time to AZA start was 3·0 (IQR 1·0-13·2) months (mo), median follow-up time from AZA start was 10.6 (IQR 4·0-21·1) mo, 894 pts received AZA as first line trt, median age at AZA start was 73 (range 23-99) years. In total, 13956 AZA cycles were applied, median duration of AZA trt was 5·0 (IQR 1·9-12·1) mo, median AZA dose was 875 (IQR 700-1000) mg/cycle, AZA was applied for a median of 7 (IQR 5-7) days. Median time to best response was 3·7 (IQR 2·0-5·9) months. Early mortality was 5.5% within 30 days. During AZA trt 1225 BM evaluations (BME) were performed in 697 (48·4%) of pts. Of these, 204 achieved CR/CRi. Irrespective of BME, 622 (43%) of 1441 pts achieved an HI and 264 (18·3%) of 1441 pts achieved a PB-CR. Pts achieving CR had longer adjusted OS (23·7 vs 19·7 mo, p=0·0227; HR=0·621 [0·413-0·936]) and TTNT (19·4 vs 15·7 mo, p=0·0262; HR=0·644 [0·436-0·949] ) than pts achieving CRi. Among pts achieving CR, those additionally achieving PB-CR had longer adjusted OS (24·8 vs 16·3; p=0·0040; HR=0·256 [0·101-0·647]; Fig 1A) and TTNT (21·2 vs 11·0; p=0·0005; HR=0·219 [0·094-0·513] ; Fig 1B) than those who did not. Among pts not achieving CR, those additionally achieving PB-CR had longer adjusted OS (20·8 vs 14·1; p & lt;0·0001; HR=0·510 [0·397-0·657]; Fig 1A) and TTNT (17·7 vs 10·9; p & lt;0·0001; HR=0·485 [0·357-0·589]; Fig 1B) than those who did not. Among all pts, irrespective of BM blast count, achievement of PB-CR resulted in longer adjusted OS (21·7 vs 10·0 mo; p & lt;·0001; HR 0·363; Fig 1C) and TTNT (18.5 vs 7.8 mo; p & lt;0.0001; HR=0.346; Fig 1D) and provided added value to CR and CR/CRi. Among all response types and after MVA, the highest prognostic impact on both OS and TTNT was observed when achieving PB-CR or CR/CRi by cycle 9 or 10 (Fig 2A-B). Conclusions Above data indicate that achievement of PB-CR is a strong predictor of OS and TTNT that provides additional information to current response criteria. Inclusion of PB-CR in updated response criteria of pts with MDS, CMML or AML receiving non-intensive trt should be considered. The greatest advantage of PB-CR is that it can be easily, nearly painlessly and quickly assessed. Inclusion of PB-CR as an endpoint in clinical trials would be desirable for validation of these results. Figure 1 Figure 1. Disclosures Pleyer: AbbVie, BMS, Novartis: Honoraria, Other: Travel Sport. Pfeilstocker: BMS: Honoraria. Stauder: Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Heibl: BMS: Honoraria. Sill: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hartmann: Celgene, Amgene, Janssen, AbbVie: Honoraria. Petzer: Kite-Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: 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; Saegen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: 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; Celgene-BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees. Geissler: BMS: Honoraria. Sperr: AbbVie, BMS-Celgene, Daiichi Sankyo, Deciphera, Incyte, Jazz, Novartis, Pfizer, StemLine, Thermo Fisher: Honoraria, Research Funding. Leisch: Honoraria from BMS, Celgene, Gilead, Takeda and Novartis; Travel support: Celgene and Novartis: Honoraria, Other: Travel support. Melchardt: Abbvie, Celgene, Novartis: Honoraria. Zebisch: Novartis: Consultancy; AbbVie: Consultancy; Celgene: Consultancy, Honoraria. Machherndl-Spandl: AbbVie, Celgene, BMS, Pfizer: Honoraria. Wolf: Roche: Honoraria, Research Funding; MSD: Honoraria, Research Funding; BMS-Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Takeda: Honoraria; Gilead: Honoraria; Incyte: Honoraria; GEMOAB: Honoraria. Greil: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Daiichi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Sandoz: Honoraria, Research Funding. OffLabel Disclosure: Azacitidine is approved for all types of MDS and CMML as well as low blast count AML by FDA, but not for all subtypes of MDS and CMML by EMA.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-145401

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 3821-3821

Abstract: Background In myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML), achievement of morphologic complete response (CR) is a prerequisite for potential cure. In AML, CR is deemed the major outcome associated with improved overall survival (OS); patients (pts) without CR are considered non-responders, and hematologic improvement (HI) without bone marrow blast (BMB) clearance is considered treatment (trt) failure (Cheson 2003). Evidence suggests that these definitions may not be applicable to older pts treated with hypomethylating agents (HMA), and that achievement of CR may not be necessary for prolonged OS (Pleyer 2013, 2014, 2015; Schuh 2015; Bloomfield 2018). IWG response criteria for HI do not differentiate between pts who qualify for response (QFR) vs those that do not. Pts with 'normal' blood counts at trt start are per definition HI non-responders. This may obscure potential survival benefits of responding pts. Aims 1) Assess the impact of HI irrespective of BMB clearance and excluding immortal time bias via landmark analyses. 2) Differentiate between pts who QFR, and those with 'normal' baseline values (not-QFR) defined according to IWG prerequisites for CR. 3) Introduce 3 new categories of HI: peripheral blood blasts (PBB), elevated white blood cells (WBC), and PB-CR (defined as Hb ≥11 g/dl, ANC ≥1.0 G/l, WBC 〈 15 G/l, PB blasts: 0%) in analogy to the concept of complete hematologic response in chronic myelogenous leukemia. Methods 1301 consecutive pts with azacitidine (AZA) trt were analyzed (NCT01595295). Data cut-off 26.07.19. HI was assessed according to IWG criteria (Cheson 2006) and the definitions specified in 3) above. More recent proposals of revision for low-risk MDS pts included in trials (Platzbecker 2018) remain largely idem. Human errors in HI assessment for each AZA cycle and lineage were excluded by automated computational calculation from electronic case report form (eCRF) data. Landmark analyses were performed at 3 months (mo) (HI requires ≥8 weeks response duration) and 6 mo (91, 92 and 88% of MDS, CMML and AML pts respond by cycle 6 [Silverman 2011; Pleyer 2013, 2014]). Statistics were performed by Unidata Geodesign GmbH using DeployR Open 8.0.0. Results In total, 462, 113, and 720 pts had MDS, CMML and AML (n=6 unknown). At AZA start, median age was 73 (range 23-93) years. One, 2 or 3 cytopenias were present in 25, 41 and 29% of pts and 46% were transfusion dependent. 55% received AZA 1st line (26% of whom received prior growth factors or iron chelators). Median AZA dose was 889 mg/cycle and 73 mg/m2/day. Median time to 1st response was 3.0 mo and 95% of pts responded by cycle 6. During AZA trt 1091 BM evaluations (BME) were performed in 599 (46%) pts. At the 3 (6) mo landmark, 44% (47%) of pts with BME achieved CR or CR with incomplete blood count recovery (CRi). Early mortality was 5.6 and 10.3% at 30 and 60 days. Of 932 (598) pts that met the 3 (6) mo landmark, a total of 39% (25%) had no BME. The impact of HI on OS became smaller the later the landmark (Tables 1 and 2). The impact of response on OS was 0.4-4.4 mo longer and significance at the 6 mo landmark was retained using IWG criteria with (Table 1) vs without (Table 2) differentiating between pts who did or did not QFR. Pts who did not QFR had similar or better OS compared with responders. At the 3 mo landmark, proposed additional response parameters HI-PBB, HI-elevated WBC and PB-CR were assoc. with a survival benefit of +7.4, +5.0 and +12.9 mo (Table 1, Fig 1A-C). Conclusions 1) The impact of HI on OS is overestimated without landmark analyses. Median time to 1st response was 3.0 mo and ≥8 weeks response duration required. We therefore suggest using a 3 mo landmark when assessing HI. 2) Using IWG criteria for HI assessment underestimates the impact of response, as non-responders are diluted by pts who do not QFR. Distinguishing QFR/not-QFR seems necessary. 3) Proposed additional HI categories (HI-PBB, HI-elevated WBC, PB-CR) add value to current response criteria. It is often the case that BME are not performed in elderly pts in real-world settings (Dinmohamed 2015; current study). Achievement of HI in any lineage and especially PB-CR might be used as a surrogate for response in pts unable or unwilling to undergo BME for response assessment. This large and growing database is suitable to allow future validation of potential novel response criteria. Disclosures Pleyer: Celgene: Other: Advisory board; Novartis: Other: Advisory board; Inflection Point Biomedical Advisors: Other: Advisory board; Agios: Other: Advisory board; Abbvie: Other: Advisory board. Pfeilstocker:Novartis: Consultancy, Honoraria; Janssen-Cilag: Honoraria; Celgene: Consultancy, Honoraria. Stauder:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Teva (Ratiopharm): Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board, Research Funding. Heibl:Daiichi Sankyo: Honoraria; Pfizer: Honoraria; Mundipharma: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: 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; AOP Orphan Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sill:Astex: Other: Advisory board; Novartis: Other: Advisory board; AbbVie: Other: Advisory board; Astellas: Other: Advisory board. Girschikofsky:Pfizer: Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria. Petzer:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Personal fees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Vallet:MSD: Honoraria; Pfizer: Honoraria; Roche Pharmaceuticals: Consultancy. Geissler:Abbvie: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; AstraZeneca: Honoraria; AOP: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Roche: Honoraria; Ratiopharm: Honoraria. Sperr:Novartis: Honoraria; Celgene: Consultancy, Honoraria. Leisch:Novartis: Honoraria, Other: Travel support; Celgene: Other: Travel support; Bristol-Myers-Squibb: Honoraria. Egle:Celgene: Honoraria, Other: Advisory board and Travel support. Melchardt:MSD: Honoraria; Merck: Honoraria, Research Funding; Takeda: Honoraria; Janssen-Cilag: Honoraria; Roche: Honoraria; Novartis: Honoraria; Cephalon: Research Funding. Piringer:Amgen: Research Funding; Roche: Other: Travel support; Merck: Other: Travel support; Bayer: Research Funding. Zebisch:Roche: Honoraria; Novartis: Honoraria, Other: Advisory board; Celgene: Honoraria; AbbVie: Other: Advisory board. Machherndl-Spandl:Celgene: Other: Advisory board. Wolf:Celgene: Honoraria, Research Funding; Abbvie: Honoraria. Keil:Bionorica: Honoraria, Research Funding; Roche: Honoraria; Pfizer: Honoraria; Celgene: Honoraria; AbbVie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Daiichi Sankyo: Honoraria; Novartis: Honoraria; Merck: Honoraria, Research Funding; Takeda: Honoraria, Research Funding. Greil:Ratiopharm: Research Funding; MSD: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; Novartis: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Cephalon: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; Gilead: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; Pfizer: Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; Genentech: Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Eisai: Honoraria; Mundipharma: Honoraria, Research Funding; Sanofi Aventis: Honoraria; Takeda: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; GSK: Research Funding; Sandoz: Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Janssen-Cilag: Honoraria; Amgen: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; Roche: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; Boehringer Ingelheim: Honoraria. OffLabel Disclosure: Azacitidine is not approved for the treatment of MP-CMML, CMML with 〈 10% BM blasts and IPSS low-risk MDS in the EU

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-128153

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Leukemia Research, Elsevier BV, Vol. 38, No. 4 ( 2014-04), p. 475-483

Type of Medium: Online Resource

ISSN: 0145-2126

URL: Article

DOI: 10.1016/j.leukres.2014.01.006

Language: English

Publisher: Elsevier BV

Publication Date: 2014

detail.hit.zdb_id: 2008028-1

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2284-2284

Abstract: Background Approximately 10% of cases of acute myeloid leukemia (AML) arise following exposure to chemotherapy (treatment-related AML [tAML]). Compared to de novo AML patients, tAML patients have a poor prognosis, not least due to a higher proportion having adverse cytogenetics. Treatment options for tAML patients are limited and outcomes remain dismal. Median overall survival (OS) of 6.9 mo as of initial presentation, with 25% deaths within one month of diagnosis, was reported for a large cohort of tAML patients, with individualized treatments ranging from supportive care, to intensive chemotherapy (IC) and bone marrow (BM) transplantation.1 Few studies have assessed azacitidine (AZA) in patients with tAML, and those that have, did not report separate outcomes for this subgroup.2–4 Methods Here, we compare a subgroup of tAML patients (n=27) with patients with other World Health Organization (WHO)-AML subgroups (n=319) from the Austrian AZA Registry. The aim of the registry was to gain insight of the use, safety and efficacy of AZA in ‘real-world’ AML patients. The sole inclusion criteria were the diagnosis of WHO-AML and treatment with ≥1 dose of AZA. Results Baseline characteristics were compared between patients with tAML and WHO-AML: median age, gender, percentage with myelodysplatic syndrome (MDS)-related features, serum lactate dehydrogenase (LDH) level, and median peripheral blood and BM blasts were similar between both cohorts. However, tAML patients had poorer Eastern Cooperative Oncology Group Performance Status (ECOG PS) scores, more comorbidities, and a higher proportion of high-risk cytogenetics compared with WHO-AML patients. Of patients with tAML, 41% received AZA as 1st line therapy and 59% received AZA as ≥2nd line therapy. Baseline characteristics of these two subgroups were also comparable, except that tAML patients treated with AZA 1st line were older, had poorer ECOG PS and worse cytogenetics than ≥2nd line patients, which is in line with what would be expected from a cohort not deemed eligible for IC (Figure 1). Median number of AZA cycles was 4 (range 1–25) for tAML patients and 4 (range 1–46) for WHO-AML patients. Median time from AZA stop to death was 1.9 vs 1.8 mo for patients with tAML vs other WHO-AML subgroups. The overall response rate (ORR; International Working Group [IWG] 2003 criteria5) as well as the rate of hematologic improvement (HI; IWG 2006 criteria6) were similar for patients with tAML vs WHO-AML treated with AZA (complete response [CR] + CR with incomplete blood count recovery [CRi] + partial response [PR] : 22.2 vs 29.5%; and HI: 58.8 vs 57.7%, respectively; Figure 1). Median OS was similar for patients with tAML vs WHO-AML (8.9 vs 9.4 mo; p=0.147; Figure 1), but was longer for responders than non-responders in both groups of patients. Relapse-free survival was 7.7 vs 9.1 mo for patients with tAML vs WHO-AML. In univariate analyses, baseline factors that significantly affected OS for tAML patients were LDH 〉 225IU/L (p 〈 0.001) and white blood cell count ≥10G/L (p 〈 0.001; Figures 2a, b). Patients with tAML who received AZA 1st line achieved a significantly higher ORR than those who received AZA ≥2nd line (36.4 vs 12.5%; p 〈 0.001). Median time to AZA start as of initial diagnosis was 0.7 and 5.1 mo for tAML patients treated with AZA 1st line or ≥2nd line, respectively. Median number of AZA cycles was 6 (1–25) for AZA 1st line vs 4 (1–15) for AZA ≥2nd line. Median OS was not significantly different for tAML patients treated with AZA 1st vs ≥2nd line (9.0 vs 7.5 mo; p=0.717; Figure 1). Median relapse-free survival was 7.7 and 7.4 mo for AZA 1st line and ≥2nd line, respectively. tAML patients achieving CR/CRi/PR had a median OS of 16.1 mo with AZA 1st line and 12.8 mo for AZA ≥2nd line. Conclusions This represents the largest study reporting outcomes of tAML patients treated with AZA. Survival of tAML patients with AZA was comparable to that achieved in other WHO-AML subgroups, suggesting that AZA is a feasible treatment option for this poor prognostic subgroup. The OS data compare favorably to OS data reported for IC1 and are encouraging. Based on these ‘real-world’ data, randomized trials should assess AZA in tAML patients. 1. Smith SM, et al. Blood 2003;102:43–52 2. Bally C, et al. Leuk Res 2013;37:637–40 3. Fianchi L, et al. J Hematol Oncol 2012;5:44 4. Pleyer L, et al. Ann Hematol 2014; epub ahead of print 5. Cheson BD, et al. J Clin Oncol 2003;21:4642–9 6. Cheson BD, et al. Blood 2006;108:419–25 Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pleyer: Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; AOP Orphan Pharmaceuticals: Honoraria; Celgene: Consultancy, Honoraria. Off Label Use: Vidaza (azacitidine) is indicated for the treatment of adult AML patients who are not eligible for haematopoietic stem cell transplantation with 20–30 % blasts and multi-lineage dysplasia, according to WHO classification. This cohort also includes AML-patients with 〉 30% bone marrow blasts.. Burgstaller:AOP Orphan Pharmaceuticals: Honoraria; Novartis: Honoraria; Mundipharma: Honoraria; Celgene: Consultancy. Stauder:Celgene: Consultancy, Honoraria, Research Funding; Ratiopharm: Honoraria, Research Funding; Novartis: Research Funding. Girschikofsky:Pfizer: Honoraria, Research Funding; Mundipharm: Consultancy, Honoraria. Pfeilstöcker:Janssen-Cilag: Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Lang:Celgene: Consultancy. Sperr:Phadia: Research Funding; Novartis: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Valent:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Greil:Sanofi Aventis: Honoraria; Roche: Honoraria; Pfizer: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria; Astra-Zeneca: Honoraria; Novartis: Honoraria; Genentech: Honoraria, Research Funding; Janssen-Cilag: Honoraria; Merck: Honoraria; Mundipharma: Honoraria, Research Funding; Eisai: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; GSK: Research Funding; Ratiopharm: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.2284.2284

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3681-3681

Abstract: Background Few data exist reporting the incidence of World Health Organization (WHO)-defined acute myeloid leukemia (AML) subgroups in adults in Europe,1 but the incidence of AML with myelodysplastic-related features (MRF) may be higher than initially reported.2–4 Whether the presence of multilineage dysplasia has an independent prognostic impact in AML is still controversial.5,6 However, AML patients with preceding myelodysplastic syndrome (MDS)/myeloproliferative neoplasm and/or MDS-related cytogenetics (Medical Research Council [MRC]) have been shown to have poorer survival than AML-not otherwise specified (NOS).7 Previous studies of AML patients treated with azacitidine (AZA) included AML-MRF patients, but did not report on outcomes separately.3,4, 8–12 Methods Due to the lack of data assessing the prognostic impact of AML-MRF in elderly AML patients treated with AZA, we analyzed patients with AML-MRF from the Austrian AZA Registry, which was initiated to gain a comprehensive view of the safety and efficacy of AZA in ‘real-life’ patients. Similar to the approach taken by others who assessed the effect of AML-MRF irrespective of treatment modality,7 patients with AML and recurrent cytogenetic abnormalities (RCA), and treatment-related AML (tAML) based on the WHO 2008 classification13 were excluded, as these subsets have particularly good (AML-RCA) or dismal prognosis (tAML), respectively. Results The AML-MRF group comprised 217 patients (AZA 1st line, n=121; AZA ≥2nd line, n=96) and the AML-NOS group comprised 90 patients (AZA 1st line, n=33; AZA ≥2nd line, n=57). Baseline characteristics were comparable except AML-MRF patients had worse Hematopoietic Cell Transplant Comorbidity Index (HCT-CI) scores and a higher proportion of high-risk cytogenetics (Figure 1). The latter is expected as most high-risk cytogenetic abnormalities are defined as MDS-related.13 Median time from diagnosis to AZA start was 〈 1 month for AZA 1st line and 〉 6 months for AZA ≥2nd line. The median number of AZA cycles was 4 (range 1–35) for AML-MRF patients and 4.5 (range 1–46) for AML-NOS patients. The overall response rate (ORR)14 was similar for AML-MRF vs AML-NOS patients (complete response [CR] + CR with incomplete blood count recovery [CRi] + partial response [PR]: 29.0 vs 33.3%, respectively; p=0.586). Rates of hematologic improvement15 were similar for AML-MRF vs AML-NOS patients (57.9 vs 57.4%; p=0.964). Median duration of response was 7.0 vs 5.5 mo, respectively. ORR was similar for AML-MRF and AML-NOS patients irrespective of AZA treatment line (Figure 1). Median overall survival (OS) for AML-MRF vs AML-NOS patients was 9.4 vs 9.7 mo for the total cohort (p=0.490; Figure 2), and 13.1 vs 10.8 mo for patients treated with AZA 1st line. For responding patients, median OS, response duration and relapse-free survival were numerically longer for AML-MRF than AML-NOS patients within the total cohort (17.1 vs 12.6; 7.0 vs 5.5; and 9.8 vs 8.5 mo), and even more so in the AZA 1st line cohort (19.7 vs 12.6; 7.4 vs 3.9; and 10.5 vs 7.9 mo). In univariate analyses, baseline factors that significantly negatively impacted OS in AML-MRF patients treated with AZA were peripheral blood blasts 〉 0% (p=0.025), Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2 (p=0.004), 〉 3 comorbidities (p=0.004), and poor cytogenetics (p=0.001). Notably, none of these factors showed statistical significance for AML-NOS patients. Conclusions This represents the first and largest report comparing outcomes of AML-MRF vs AML-NOS patients treated with AZA. Outcomes of AML-MRF patients were similar to patients with other AML-NOS subgroups. AZA seems a feasible treatment option for these patients despite the reported poor prognostic impact of MRF. 1. Sant M, et al. Blood 2010;116:3724–34 2. Quintas-Cardama A, et al. Blood 2012;120:4840–5 3. Pleyer L, et al. Ann Hematol 2014 [Epub ahead of print] 4. Thepot S, et al. Am J Hematol 2014;89:410–6 5. Wandt H, et al. Blood 2008;111:1855–61 6. Gahn B, et al. Leukemia 1996;10:946–51 7. Miesner M, et al. Blood 2010;116:2742–51 8. van der Helm L, et al. Leuk Res 2013;37:877–82 9. Gavillet M, et al. Haematologica 2012;97:1929–31 10. Maurillo L, et al. Cancer 2012;118:1014–22 11. Ivanoff S, et al. Am J Hematol 2013;88:601–5 12. Al-Ali HK, et al. Leuk Lymphoma 2011;53:110–7 13. Swerdlow SH, et al. IARC press 2008 14. Cheson BD, et al. J Clin Oncol 2003;21:4642–9 15. Cheson BD, et al. Blood 2006;108:419–25 Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pleyer: Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; AOP Orphan Pharmaceuticals: Honoraria; Celgene: Consultancy, Honoraria. Off Label Use: Vidaza (azacitidine) is indicated for the treatment of adult AML patients who are not eligible for haematopoietic stem cell transplantation with 20–30 % blasts and multi-lineage dysplasia, according to WHO classification. This cohort also includes AML-patients with 〉 30% bone marrow blasts. Burgstaller:AOP Orphan Pharmaceuticals: Honoraria; Novartis: Honoraria; Mundipharma: Honoraria; Celgene: Consultancy. Stauder:Novartis: Research Funding; Ratiopharm: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Girschikofsky:Pfizer: Honoraria, Research Funding; Mundipharm: Consultancy, Honoraria. Pfeilstöcker:Janssen-Cilag: Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Lang:Celgene: Consultancy. Sperr:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Phadia: Research Funding. Valent:Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Greil:Sanofi Aventis: Honoraria; Roche: Honoraria; Pfizer: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria; Astra-Zeneca: Honoraria; Novartis: Honoraria; Genentech: Honoraria, Research Funding; Janssen-Cilag: Honoraria; Merck: Honoraria; Mundipharma: Honoraria, Research Funding; Eisai: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; GSK: Research Funding; Ratiopharm: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.3681.3681

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: American Journal of Hematology, Wiley, Vol. 92, No. 10 ( 2017-10)

Abstract: The aim of this study was to evaluate the efficacy and feasibility of intensified consolidation therapy employing fludarabine and ARA‐C in cycle 1 and intermediate‐dose ARA‐C (IDAC) in cycles 2 through 4, in elderly acute myeloid leukemia (AML) patients and to analyze the effects of pegfilgrastim on the duration of neutropenia, overall toxicity, and hospitalization‐time during consolidation in these patients. Thirty nine elderly patients with de novo AML (median age 69.9 years) who achieved complete remission (CR) after induction‐chemotherapy were analyzed. To examine the effect of pegfilgrastim on neutropenia and hospitalization, we compared cycles 2 and 4 where pegfilgrastim was given routinely from day 6 (IDAC‐P) with cycle 3 where pegfilgrastim was only administered in case of severe infections and/or prolonged neutropenia. All four planned cycles were administered in 23/39 patients (59.0%); 5/39 patients (12.8%) received 3 cycles, 3/39 (7.7%) 2 cycles, and 8/39 (20.5%) one consolidation‐cycle. The median duration of severe neutropenia was 7 days in cycle 2 (IDAC‐P), 11.5 days in cycle 3 (IDAC), and 7.5 days in cycle 4 (IDAC‐P) ( P   〈  .05). Median overall survival was 1.1 years and differed significantly between patients aged 〈 75 and ≥75 years ( P   〈  .05). The probability to be alive after 5 years was 32%. Together, intensified consolidation can be administered in AML patients ≥60, and those who are 〈 75 may benefit from this therapy. Routine administration of pegfilgrastim during consolidation shortens the time of neutropenia and hospitalization in these patients.

Type of Medium: Online Resource

ISSN: 0361-8609 , 1096-8652

URL: Issue

URL: Article

DOI: 10.1002/ajh.v92.10

DOI: 10.1002/ajh.24847

Language: English

Publisher: Wiley

Publication Date: 2017

detail.hit.zdb_id: 1492749-4

In: International Journal of Molecular Sciences, MDPI AG, Vol. 18, No. 2 ( 2017-02-15), p. 415-

Type of Medium: Online Resource

ISSN: 1422-0067

URL: Article

DOI: 10.3390/ijms18020415

Language: English

Publisher: MDPI AG

Publication Date: 2017

detail.hit.zdb_id: 2019364-6

SSG: 12