Search

Paiva: SkylineDx: Consultancy; Takeda: Consultancy, Honoraria, Research Funding; Roche: Research Funding; Adaptive: Honoraria; Amgen: Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Kite: Consultancy; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding. Alonso Dominguez:Celgene: Research Funding; Incyte: Research Funding; Pfizer: Research Funding. Martinez-Lopez:Janssen: Speakers Bureau; Altum: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Hosea: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Roche: Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Vivia Biotech: Honoraria; Novartis: Research Funding; BMS: Research Funding, Speakers Bureau; Incyte: Research Funding, Speakers Bureau. Sossa:Astellas: Honoraria; Roche: Honoraria; Takeda: Honoraria; Novo: Honoraria. San-Miguel:Roche, AbbVie, GlaxoSmithKline, and Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb, Celgene, Novartis, Takeda, Amgen, MSD, Janssen, and Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Background:Evaluation of MRD is standard in patients with AML. However, the role of decentralized MRD assessment for risk stratification in AML remains largely unknown, and so it does which methodological aspects are critical to empower the evaluation of MRD with prognostic significance, particularly if using MFC.

Although consensus guidelines have been proposed in 2010 for the diagnostic screening of paroxysmal nocturnal hemoglobinuria (PNH) by flow cytometry (FCM), so far no study has investigated the efficiency of such medical indications in multicentric vs. reference laboratory settings. Here we evaluate the efficiency of consensus medical indications for PNH testing in 3,938 peripheral blood samples submitted to FCM testing in 24 laboratories in Spain and one reference center in Brazil. Overall, diagnostic screening based on consensus medical indications was highly efficient (14% of PNH+samples) both in the multicenter setting in Spain (10%) and the reference laboratory in Brazil (16%). The highest frequency of PNH+cases was observed among patients screened because of bone marrow (BM) failure syndrome (33%), particularly among those with aplastic anemia (AA; 45%) and to a less extent also a myelodysplastic syndrome (MDS; 10%). Among the other individuals studied, the most efficient medical indications for PNH screening included: hemolytic anemia (19%), hemoglobinuria (48%) and unexplained cytopenias (9%). In contrast, only a minor fraction of the patients who had been submitted for PNH testing because of unexplained thrombosis in the absence of cytopenia, were positive (0.4%). In summary, our results demonstrate that the current medical indications for PNH screening by FCM are highly efficient, although improved screening algorithms are needed for patients presenting with thrombosis and normal blood cell counts. © 2016 International Clinical Cytometry Society

Introduction

Sanchez: Amgem: Other: travel grants; Janssen: Other: travel grants; Roche: Other: travel grants; Abbvie: Other: travel grants; Celgene: Other: travel grants. Tormo:Roche: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; MSD: Honoraria; Daiichi Sankyo: Honoraria.The objective of our study is to retrospectively analyze the efficacy of the off-label use of venetoclax in patients with recurrent or refractory acute myeloid leukemia

Introduction

Introduction:Acute myeloblastic leukaemia (AML) is an heterogeneous disease with different molecular and prognostic characteristics. According to the comorbidities and the revised 2017 European Leukaemia genetic risk stratification (ELN17), allogeneic hematopoietic cell transplantation (HCT) is the best therapeutic option for many patients with AML (Grimm, Blood Adv 2020). However, relapse remains the main cause of mortality after transplantation. Impact of MRD on the outcome of patients is well recognized and ELN2017 introduced the new response category complete remission (CR) without MRD (Döhner H, Blood 2017). Detection of measurable residual disease (MRD) by multiparameter flow cytometry (MFC) in AML before allogeneic HCT could be a powerful predictor of outcome and decisive when establishing strategies that modify the prognosis of these patients. Methods: Retrospective multicentre analysis of MRD by MFC of patients undergoing transplantation allogeneic in 4 centres during the period from 2012 to 2020. Both Leukaemia Associated Aberrant Immunophenotype (LAIP) and different from normal (DFN) approach were used to analyse the MRD. The MRD was carried out with 8-color panels based on Euroflow protocols. The samples were acquired in 8-color digital cytometers (FACSCanto II) calibrated and compensated according to Euroflow protocols. Results: 295 of 318 patients were evaluated. Table 1 shows the characteristics of the patients. 285 (96.7%) were in complete remission (CR), 207 had negative MRD, in 21 MRD was less than 0.1% (MRD-low) and in 57 greater than or equal to 0.1% (MRD-high). At 2 years, the overall survival (OS) and leukaemia-free survival (LFS) in the whole group were 69% (95% CI 63.18-74.18) and 58.4% (95% CI 52.4-63.9) respectively. In CR patients, MRD levels significantly influenced on outcomes, with OS and LFS of 76.7% and 67.6% for negative MRD, 68.5% and 49.7% MRD-low and 50 % and 36.6% in MRD-high, p <0.001) (Figure 1). Considering only MRD-high as positive, according to ELN17, cumulative incidence of relapse (CIR) at 2 and 5 years were significantly lower among those with positive MRD: 22% (95% CI 17-28.1%) and 27% (95% CI 21%-33.5%) for negative MRD vs 46,5% (95% CI 32.4%-59.5%) and 50% (95% CI 34.8%-63.2%) in positive MRD, p 0.0005. No differences were observed in terms of non relapse mortality (p 0.2).. Likewise, positive MRD also identified different prognostic subgroups within the ELN2017 subgroups: OS and LFS among high-risk ELN2017 patients of 63.6% and 52.3% in negative MRD vs 35.7% and 18.2% in positive MRD patients, p = 0.0085 and p = 0.0094, respectively; for intermediate risk: 77% and 67.6% in negative MRD vs 67% and 50.5% in positive MRD patients, p = 0.23 and p = 0.056; and for favourable: 84% and 77.7% in negative MRD vs 48% and 39.2% in patients with positive MRD, p = 0.0051 and p = 0.0341. Considering the conditioning regimen, patients with MRD negative before transplant had better OS and LFS at 2 years (82% and 71.4% among those received myeloablative conditioning and 65% and 57.6% among those who received reduced intensity, respectively) than those who had positive MRD prior to transplant (56% and 44.4% in myeloablative and 43% and 25.5% in reduced intensity) (p <0.001) (Figure 2). In multivariate time-dependent analysis, age (HR 1.019 p = 0.024-95% CI 1.001-1,038), adverse risk group according to ELN17 (HR 2.13 p = 0.033 CI95 1.54-3.93 ) and MRD before transplant (HR 3.8 p <0.001 95 CI 1.55-3.93) significantly influenced survival. Conclusions: Detection of MRD prior to transplant by MFC identifies a group of patients with a worse prognosis and could be key when selecting the most appropriate therapeutic strategy.

Caballero: Celgene: Consultancy. Belén Vidriales: Roche: Consultancy; Novartis: Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Astellas: Consultancy, Speakers Bureau. Montesinos: Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Stemline/Menarini: Consultancy; Tolero Pharmaceutical: Consultancy; Agios: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Forma Therapeutics: Consultancy; Glycomimetics: Consultancy; Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board, Research Funding, Speakers Bureau. Perez-Simon: JANSSEN, TAKEDA, PFIZER, JAZZ, BMS, AMGEN, GILEAD: Other: honorarium or budget for research projects and/or participation in advisory boards and / or learning activities and / or conferences.

Belén Vidriales: Roche: Consultancy; Novartis: Speakers Bureau; Astellas: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau. Pérez-Encinas: Janssen: Consultancy. Tormo: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Montesinos: Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Glycomimetics: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Forma Therapeutics: Consultancy; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Stemline/Menarini: Consultancy; Tolero Pharmaceutical: Consultancy; Agios: Consultancy; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board, Research Funding, Speakers Bureau.Venetoclax for Patients with Relapsed or Refractory Acute Myeloid Leukemia

Díez-Campelo: Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Introduction. Nucleophosmin gene mutation (NPM1mut) occurs in around 30% of acute myeloid leukemia (AML) patients, frequently linked with favourable prognosis in the absence of FLT3-ITDmut, which occurs in around 40% of NPM1mutAML. Therefore, more expeditious diagnostic approaches may contribute to early diagnosis and prognostic stratification of these patients. Herein, we investigated the association of immunophenotypic features of leukemic and monocytic cells with the presence of NPM1mutin AML.

Background: CC-90009 is a novel cereblon E3 ligase modulator (CELMoD), which is currently under investigation in a first-in-human, phase I study (CC-90009-AML-001; NCT02848001) in patients with R/R AML. In preclinical models, CC-90009 drives the binding of the target protein, translation termination factor G1 to S phase transition 1 (GSPT1), to cereblon and induces its ubiquitination and proteasome-dependent degradation. Loss of GSPT1 results in activation of the integrated stress response (ISR), inhibition of nonsense-mediated decay (NMD), and induction of apoptosis. Deep degradation of GSPT1, mediated by CC-90009, led to AML cell death in vitro and potent antitumor activity in patient-derived AML xenograft models. In the ongoing phase I study, CC-90009 has demonstrated antileukemic activity. Here, we characterize the pharmacodynamic responses using a suite of novel assays to support CC-90009 dose and schedule optimization.

Fan: Celgene Corporation: Employment, Equity Ownership. Wang:Celgene Corporation: Employment. Couto:Celgene Corporation: Employment, Equity Ownership, Patents & Royalties. Yao:Celgene Corporation: Employment. Uy:Astellas: Consultancy; Pfizer: Consultancy; Curis: Consultancy; GlycoMimetics: Consultancy. Zeidan:Pfizer: Consultancy, Honoraria, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Trovagene: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Research Funding; Jazz: Honoraria; Ariad: Honoraria; Agios: Honoraria; Novartis: Honoraria; Astellas: Honoraria; Daiichi Sankyo: Honoraria; Cardinal Health: Honoraria; Seattle Genetics: Honoraria; BeyondSpring: Honoraria; Otsuka: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Acceleron Pharma: Consultancy, Honoraria, Research Funding; Medimmune/AstraZeneca: Research Funding; Celgene Corporation: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding. Montesinos:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees. DeAngelo:Jazz Pharmaceuticals, Inc.: Consultancy; Takeda Pharmaceuticals: Consultancy; Shire: Consultancy; GlycoMimetics: Research Funding; Pfizer, Inc.: Consultancy; Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; Incyte Corporation: Consultancy; Celgene Corporation: Consultancy; AbbVie, Inc.: Research Funding; Blue print Medicines: Consultancy, Research Funding; Amgen: Consultancy. Altman:Novartis: Consultancy; Cancer Expert Now: Consultancy; Biosight: Other: US Lead; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; France Foundation: Speakers Bureau; prIME Oncology: Speakers Bureau; PeerView: Speakers Bureau; Theradex: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Glycomimetics: Consultancy, Honoraria, Other: Data Safety and Monitoring Committee. Koprivnikar:Amgen: Speakers Bureau; Abbvie: Speakers Bureau; Pfizer: Honoraria; Novartis: Speakers Bureau. Vyas:Astellas: Speakers Bureau; Pfizer: Speakers Bureau; Abbvie: Speakers Bureau; Daiichi Sankyo: Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Forty Seven, Inc.: Research Funding. Fløisand:Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria; Novartis: Honoraria. Gjertsen:Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; EU Horizon 2020: Research Funding; KinN Therapeutics AS: Equity Ownership; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; BerGenBio: Consultancy, Membership on an entity's Board of Directors or advisory committees; ERA PerMed: Research Funding; The Norwegian Cancer Society: Research Funding; Helse Vest Health Trust: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Research Council of Norway: Research Funding; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; ACTII AS: Equity Ownership. Buchholz:Celgene Corporation: Employment, Equity Ownership. Pourdehnad:Celgene Corporation: Employment, Equity Ownership. Pierce:Celgene Corporation: Employment, Equity Ownership.

Uy: GlycoMimetics: Consultancy; Curis: Consultancy; Astellas: Consultancy; Pfizer: Consultancy. Montesinos:Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding. DeAngelo:Blue print Medicines: Consultancy, Research Funding; Celgene Corporation: Consultancy; Shire: Consultancy; Pfizer, Inc.: Consultancy; Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; Incyte Corporation: Consultancy; Jazz Pharmaceuticals, Inc.: Consultancy; GlycoMimetics: Research Funding; AbbVie, Inc.: Research Funding; Takeda Pharmaceuticals: Consultancy; Amgen: Consultancy. Altman:Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Biosight: Other: US Lead; France Foundation: Speakers Bureau; PeerView: Speakers Bureau; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Glycomimetics: Consultancy, Honoraria, Other: Data Safety and Monitoring Committee; Cancer Expert Now: Consultancy; Theradex: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; prIME Oncology: Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Koprivnikar:Amgen: Speakers Bureau; Pfizer: Honoraria; Abbvie: Speakers Bureau; Novartis: Speakers Bureau. Vyas:Astellas: Speakers Bureau; Abbvie: Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Forty Seven, Inc.: Research Funding; Daiichi Sankyo: Speakers Bureau; Pfizer: Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Fløisand:Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria; Novartis: Honoraria. Gjertsen:BerGenBio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees; EU Horizon 2020: Research Funding; Daiichi Sankyo: 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; The Norwegian Cancer Society: Research Funding; KinN Therapeutics AS: Equity Ownership; ACTII AS: Equity Ownership; ERA PerMed: Research Funding; Helse Vest Health Trust: Research Funding; Research Council of Norway: Research Funding. Esteve:Astellas: Consultancy, Speakers Bureau; Amgen: Consultancy; Novartis: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Roche: Consultancy; Pfizer: Consultancy. Buchholz:Celgene Corporation: Employment, Equity Ownership. Couto:Celgene Corporation: Employment, Equity Ownership, Patents & Royalties. Fan:Celgene Corporation: Employment, Equity Ownership. Hanna:Celgene Corporation: Employment, Equity Ownership. Li:Celgene Corporation: Employment, Equity Ownership. Pierce:Celgene Corporation: Employment, Equity Ownership. Hege:Celgene Corporation: Employment, Equity Ownership, Patents & Royalties; Mersana Therapuetics: Membership on an entity's Board of Directors or advisory committees; Society for Immunotherapy of Cancer: Membership on an entity's Board of Directors or advisory committees; Arcus Biosciences: Membership on an entity's Board of Directors or advisory committees. Pourdehnad:Celgene Corporation: Employment, Equity Ownership. Zeidan:Pfizer: Consultancy, Honoraria, Research Funding; Medimmune/AstraZeneca: Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Trovagene: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Research Funding; Jazz: Honoraria; Ariad: Honoraria; Agios: Honoraria; Seattle Genetics: Honoraria; BeyondSpring: Honoraria; Cardinal Health: Honoraria; Daiichi Sankyo: Honoraria; Novartis: Honoraria; Otsuka: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Acceleron Pharma: Consultancy, Honoraria, Research Funding; Celgene Corporation: Consultancy, Honoraria, Research Funding; Astellas: Honoraria.