Kooperativer Bibliotheksverbund

In: Mayo Clinic Proceedings, Elsevier BV, Vol. 90, No. 8 ( 2015-08), p. 996-1000

Type of Medium: Online Resource

ISSN: 0025-6196

URL: Article

DOI: 10.1016/j.mayocp.2015.06.001

Language: English

Publisher: Elsevier BV

Publication Date: 2015

detail.hit.zdb_id: 2052617-9

In: Journal of the National Comprehensive Cancer Network, Harborside Press, LLC, Vol. 7, No. 9 ( 2009-10), p. 984-1023

Type of Medium: Online Resource

ISSN: 1540-1405 , 1540-1413

URL: Article

DOI: 10.6004/jnccn.2009.0065

Language: English

Publisher: Harborside Press, LLC

Publication Date: 2009

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3548-3548

Abstract: Background: The diagnosis of AML requires an integrated approach of clinical, morphologic, cytogenetic, and molecular assessments. The CONNECT MDS/AML Disease Registry (NCT01688011) is a prospective, longitudinal, multicenter, observational cohort study of patients (pts) in the United States with newly diagnosed AML, MDS, or idiopathic cytopenia of undetermined significance, designed to evaluate diagnostic and treatment (Tx) patterns, clinical and pt-reported outcomes, and correlative data, such as genetic mutations. This investigation was performed to assess how pts with AML are diagnosed at community and academic sites and compare how these diagnostic practices align with WHO 2008 recommendations for AML. Methods: Pt enrollment began in December, 2013 and will continue until ~1500 pts from ~150 US sites are enrolled. Target enrollment for the AML cohort is 400 pts. To best capture the typical distribution of clinical practice settings in which AML pts are treated, ~80% of the sites will be community-based and ~20% will be academic institutions (ie, affiliated with a medical school). Pts aged ≥55 years (yrs) with newly diagnosed AML (excluding acute promyelocytic leukemia) are eligible. All decisions regarding pt care (Tx, testing) are determined by the study clinician, as the disease registry is non-interventional. AML diagnosis is confirmed by independent central review of all available diagnostic test reports, including bone marrow (BM) aspirates and biopsies, cytogenetics, molecular testing, and laboratory results. Diagnostic procedures are recorded in an electronic data capture system. Pt data will be entered quarterly for up to 8 years of follow-up. Results: Between December 12, 2013 and May 19, 2016, 180 AML pts have enrolled in the registry from 73 sites; 125 pts (69%) enrolled at a community site (including 1 governmental site) and 55 pts (31%) enrolled at an academic center. Median age of all pts was 71 yrs (range 55-91), with 72% of pts aged ≥65 yrs (Table 1). Blast percentages were reported in 97% of cases, mainly in BM, although peripheral blood blasts were also assessed for 71% of pts (Table 2). Manual differential blast count was reported for 63% of pts, and flow cytometry and immunohistochemistry were used to determine blast counts for 10% of pts each. Immunophenotyping by flow cytometry was reported for 97% of pts. Erythroid, megakaryocytic, or neutrophilic dysplasia, and presence or absence of Auer rods, ring sideroblasts, or fibrosis were reported for 〈 50% of all pts (Table 2). Conventional karyotyping was performed for 90% of pts and FISH testing was reported for 80% of pts (Table 3). Mutation testing was reported for 85 pts (47%). Conclusions: The ongoing prospective CONNECT MDS/AML registry is uniquely positioned to assess current clinical practice patterns in AML. Flow cytometry and conventional karyotyping were done in most cases; however, manual blast count was missing for 37% of AML pt samples at diagnosis. Instead, ~10% of blasts counts were evaluated by flow cytometry or immunohistochemistry, and ~18% by 'other' means (ie, blast count estimations). Flow cytometry for blast enumeration is discouraged in WHO 2008 recommendations, as it may both under- and overestimate counts. Despite a 90% rate of conventional karyotyping, FISH testing was reported for 80% of pts, suggesting FISH may be used more than is necessary. Mutation testing was reported for approximately one-half of pts, which may reflect a lack of testing, a lag in mutational test reporting, or a combination of both. Diagnostic practices for AML pts enrolled thus far appear to be guided by WHO 2008 recommendations; awareness of updated recommendations may change diagnostic patterns as new AML pts enter the CONNECT MDS/AML registry. Disclosures George: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Allakos: Research Funding; Allakos: Research Funding; Blueprint Medicines: Consultancy; Novartis: Consultancy; Seattle Genetics: Consultancy, Research Funding; Incyte: Consultancy; GLG: Consultancy; Wiley Blackwell: Consultancy; American Registry of Pathology: Patents & Royalties; Wolters Kluwer: Patents & Royalties; UpToDate: Patents & Royalties. Erba:Sunesis: Consultancy; Novartis: Consultancy, Speakers Bureau; Celator: Research Funding; Ariad: Consultancy; Jannsen: Consultancy, Research Funding; Juno: Research Funding; Astellas: Research Funding; Incyte: Consultancy, DSMB, Speakers Bureau; Agios: Research Funding; Pfizer: Consultancy; Gylcomimetics: Other: DSMB; Millennium Pharmaceuticals, Inc.: Research Funding; Celgene: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Daiichi Sankyo: Consultancy. Steensma:Amgen: Consultancy; Ariad: Equity Ownership; Millenium/Takeda: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Genoptix: Consultancy. Pollyea:Alexion: Other: advisory board; Ariad: Other: advisory board; Celgene: Other: advisory board, Research Funding; Glycomimetics: Other: DSMB member; Pfizer: Other: advisory board, Research Funding. Abedi:Celgene: Consultancy. Bejar:Genoptix: Consultancy. Grinblatt:Celgene Corporation: Consultancy, Speakers Bureau. Komrokji:Novartis: Consultancy, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Revicki:Celgene: Consultancy. Roboz:Cellectis: Research Funding; Agios, Amgen, Amphivena, Astex, AstraZeneca, Boehringer Ingelheim, Celator, Celgene, Genoptix, Janssen, Juno, MEI Pharma, MedImmune, Novartis, Onconova, Pfizer, Roche/Genentech, Sunesis, Teva: Consultancy. Savona:TG Therapeutics: Research Funding; Takeda: Research Funding; Amgen Inc.: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Sunesis: Research Funding; Ariad: Membership on an entity's Board of Directors or advisory committees. Scott:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sekeres:Millenium/Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Thompson:VIA Oncology: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Multiple Myeloma International Registry; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: MDS/AML Registry; Doximity: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; AIM Specialty Health: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Fliss:Celgene Corporation: Employment, Equity Ownership. Swern:Celgene: Employment, Equity Ownership. Nifenecker:Celgene: Employment, Equity Ownership. Kiselev:Celgene: Employment, Equity Ownership. Sugrue:Celgene Corporation: Employment, Equity Ownership. Foucar:Celgene: Membership on an entity's Board of Directors or advisory committees; ASCP press: Other: Book royalties; Elsevier: Other: Book royalties; Lippincott WW: Other: Book royalties.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.3548.3548

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: eJHaem, Wiley, Vol. 1, No. 1 ( 2020-07), p. 58-68

Abstract: Diagnostic and molecular genetic testing are key in advancing the treatment of acute myeloid leukemia (AML), yet little is known about testing patterns outside of clinical trials, especially in older patients. We analyzed diagnostic and molecular testing patterns over time in 565 patients aged ≥ 55 years with newly diagnosed AML enrolled in the Connect ® MDS/AML Disease Registry (NCT01688011) in the United States. Diagnostic data were recorded at enrolment and compared with published guidelines. The percentage of bone marrow blasts was reported for 82.1% of patients, and cellularity was the most commonly reported bone marrow morphological feature. Flow cytometry, karyotyping, molecular testing, and fluorescence in situ hybridization were performed in 98.8%, 95.4%, 75.9%, and 75.7% of patients, respectively. Molecular testing was done more frequently at academic than community/government sites (84.3% vs 70.2%; P  〈  .001). Enrolment to the Registry after 2016 was significantly associated with molecular testing at academic sites (odds ratio [OR] 2.59; P  = .023) and at community/government sites (OR 4.85; P  〈  .001) in logistic regression analyses. Better understanding of practice patterns may identify unmet needs and inform institutional protocols regarding the diagnosis of patients with AML.

Type of Medium: Online Resource

ISSN: 2688-6146 , 2688-6146

URL: Issue

URL: Article

DOI: 10.1002/jha2.v1.1

DOI: 10.1002/jha2.16

Language: English

Publisher: Wiley

Publication Date: 2020

detail.hit.zdb_id: 3021452-X

In: International Journal of Laboratory Hematology, Wiley, Vol. 43, No. 3 ( 2021-06), p. 426-432

Abstract: The presence of ring sideroblasts (RS) and mutation of the SF3B1 gene are diagnostic of lower‐risk (LR) myelodysplastic syndromes (MDS) and are correlated with favorable outcomes. However, information on testing and reporting in community‐based clinical settings is scarce. This study from the Connect ® MDS/AML Disease Registry aimed to compare the frequency of RS and SF3B1 reporting for patients with LR‐MDS, before and after publication of the 2016 World Health Organization (WHO) MDS classification criteria. Methods Ring sideroblasts assessment and molecular testing data were collected from patients with LR‐MDS at enrollment in the Registry. Patients enrolled between December 2013 and the data cutoff of March 2020 were included in this analysis. Results Among 489 patients with LR‐MDS, 434 (88.8%) underwent RS assessment; 190 were assessed prior to the 2016 WHO guidelines (Cohort A), and 244 after (Cohort B). In Cohort A, 87 (45.8%) patients had RS identified; 29 (33.3%) patients had RS  〈  15%, none of whom underwent molecular testing for SF3B1 . In Cohort B, 96 (39.3%) patients had RS identified; 31 (32.3%) patients had  〈  15% RS, with 13 undergoing molecular testing of which 10 were assessed for SF3B1 . Conclusions In the Connect ® MDS/AML Registry, only 32% of patients with 〈 15% RS underwent SF3B1 testing after the publication of the WHO 2016 classification criteria. There was no change in RS assessment frequency before and after publication, despite the potential impact on diagnostic subtyping and therapy selection, suggesting an unmet need for education to increase testing rates for SF3B1 mutations.

Type of Medium: Online Resource

ISSN: 1751-5521 , 1751-553X

URL: Issue

URL: Article

DOI: 10.1111/ijlh.v43.3

DOI: 10.1111/ijlh.13400

Language: English

Publisher: Wiley

Publication Date: 2021

detail.hit.zdb_id: 2268600-9

In: Transplantation and Cellular Therapy, Elsevier BV, Vol. 29, No. 7 ( 2023-07), p. 460.e1-460.e9

Type of Medium: Online Resource

ISSN: 2666-6367

URL: Article

DOI: 10.1016/j.jtct.2023.04.011

Language: English

Publisher: Elsevier BV

Publication Date: 2023

detail.hit.zdb_id: 3056525-X

In: Biomarker Research, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2023-03-16)

Abstract: Studies have not systematically compared the ability to verify performance of prognostic transcripts in paired bulk mononuclear cells versus viable CD34-expressing leukemic blasts from patients with acute myeloid leukemia. We hypothesized that examining the homogenous leukemic blasts will yield different biological information and may improve prognostic performance of expression biomarkers. Methods To assess the impact of cellular heterogeneity on expression biomarkers in acute myeloid leukemia, we systematically examined paired mononuclear cells and viable CD34-expressing leukemic blasts from SWOG diagnostic specimens. After enrichment, patients were assigned into discovery and validation cohorts based on availability of extracted RNA. Analyses of RNA sequencing data examined how enrichment impacted differentially expressed genes associated with pre-analytic variables, patient characteristics, and clinical outcomes. Results Blast enrichment yielded significantly different expression profiles and biological pathways associated with clinical characteristics (e.g., cytogenetics). Although numerous differentially expressed genes were associated with clinical outcomes, most lost their prognostic significance in the mononuclear cells and blasts after adjusting for age and ELN risk, with only 11 genes remaining significant for overall survival in both cell populations ( CEP70 , COMMD7 , DNMT3B , ECE1 , LNX2 , NEGR1 , PIK3C2B , SEMA4D , SMAD2 , TAF8 , ZNF444 ). To examine the impact of enrichment on biomarker verification, these 11 candidate biomarkers were examined by quantitative RT/PCR in the validation cohort. After adjusting for ELN risk and age, expression of 4 genes ( CEP70 , DNMT3B , ECE1 , and PIK3CB ) remained significantly associated with overall survival in the blasts, while none met statistical significance in mononuclear cells. Conclusions This study provides insights into biological information gained/lost by examining viable CD34-expressing leukemic blasts versus mononuclear cells from the same patient and shows an improved verification rate for expression biomarkers in blasts.

Type of Medium: Online Resource

ISSN: 2050-7771

URL: Article

DOI: 10.1186/s40364-023-00461-0

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 2699926-2

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4050-4050

Abstract: Background: Clinical studies have shown that some pts with CML-CP who achieve deep, sustained molecular response (MR) on BCR-ABL1 tyrosine kinase inhibitor (TKI) therapy are able to stop treatment and maintain treatment-free remission (TFR). Because more pts achieve deep MR with NIL vs IM, a higher proportion of pts on NIL may be eligible to attempt TFR. Currently, 4 studies (ENESTgoal, ENESTop, ENESTfreedom, and ENESTpath) are evaluating TFR after NIL in pts with CML-CP. ENESTgoal is an open-label phase 2 study of TFR after second-line NIL in pts who achieved major MR (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [IS]) but not MR4.5 (BCR-ABL1IS ≤ 0.0032%) on IM. The MMR to MR4.5 eligibility window was based on the assumption that approximately one-third of pts within this range of MR would achieve MR4.5 within 2 years of switching to NIL on study. Due to slow enrollment and a higher than expected screen failure rate (primarily due to pts not being in the specified MR window), the sample size was reduced to 59 pts, and the NIL consolidation phase was changed to 2 years (Figure). Methods: Adult (aged ≥ 18 years) pts with Philadelphia chromosome-positive CML-CP who achieved MMR but not MR4.5 (confirmed in a central laboratory) after ≥ 1 year of IM therapy were switched to NIL 300 mg twice daily (BID) upon enrollment. On study, pts who achieve MR4.5 within 2 years of switching to NIL and maintain deep MR during a subsequent 2-year NIL consolidation phase are then eligible to attempt TFR (ie, stop NIL). Approximately 20 pts are expected to become eligible to attempt TFR. Real-time quantitative polymerase chain reaction (RQ-PCR) monitoring is performed by a central laboratory every 3 months on study and more frequently during the TFR phase. During the TFR phase, pts with loss of MMR (per protocol amendment) are required to re-initiate NIL. The primary endpoint is the molecular relapse-free rate 6 months after attempting TFR. Herein we present an early analysis of pts who switched from IM to NIL in ENESTgoal. Results: Fifty-nine pts were enrolled by January 9, 2015 (median age, 54 years [range, 26-74 years]); 66% of pts were male, and80% were Caucasian. Baseline Sokal risk scores were as follows: high, 5 pts (9%); intermediate, 9 pts (15%); low, 32 pts (54%); unknown, 13 pts (22%). Median prior IM treatment duration was 64 months (range, 13-163 months). As of the data cutoff date (March 30, 2015), 49 pts (83%) were on study (monitoring phase, n = 32; consolidation phase, n = 16; TFR phase, n = 1), and 10 pts (17%) had discontinued (monitoring phase, n = 8; consolidation phase, n = 2). Reasons for study discontinuation included withdrawn consent (n = 4), adverse events (AE; n = 2 [grade 1 transient ischemic attack and grade 4 pericardial effusion]), unsatisfactory therapeutic effect (n = 2), administrative problems (n = 1), and abnormal laboratory values (n = 1). The median NIL treatment duration on study was 11.5 months (range, 2.7-18.5 months). AEs were reported in 56 pts (95%), the majority of which were low grade. Grade 3/4 AEs included elevated lipase (10%); rash (3%); and elevated amylase, hypophosphatemia, bronchospasm, headache, hyperglycemia, leukocytosis, non-cardiac-related chest pain, small-intestinal obstruction, squamous cell carcinoma, pericardial effusion, and vomiting (2% each). NIL-related AEs (≥ 5%; all-grade) included rash (27%); fatigue (14%); pruritus (12%); lipase increased (10%); abdominal pain and constipation (8% each); fatigue, headache, and palpitations (7% each); and abdominal discomfort, alopecia, nausea, and weight decreased (5% each). There were no QTcF values 〉 500 ms and no deaths. A total of 19 pts (32%) achieved confirmed MR4.5, and the median time to MR4.5 was 119 days (range, 56-448 days). In the consolidation phase, the median follow-up was 153 days (range, 11-434 days), and the median duration of MR4.5 was 97 days (range, 11-434 days). Per the original protocol, 1 pt entered the TFR phase after 1 year of consolidation and had BCR-ABLIS levels of 0.0241% at 60 days and 0.0216% at 90 days after attempting TFR, triggering re-initiation of NIL. Conclusion: After switching from IM to NIL, 32% of pts achieved confirmed MR4.5 with a median treatment duration of 11.5 months. Safety results are consistent with previously reported NIL studies. Results from longer-term follow-up in ENESTgoal and those from other ongoing studies will provide a better understanding of the role of NIL in enabling pts to achieve TFR. Figure 1. Figure 1. Disclosures Ritchie: Incyte: Speakers Bureau; Celgene: Speakers Bureau. Deininger:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ariad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Erba:Novartis: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Amgen: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Celgene: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Millennium/Takeda: Research Funding; Millennium/Takeda: Research Funding; Celator: Research Funding; Celator: Research Funding; Astellas: Research Funding; Sunesis: Consultancy; Astellas: Research Funding; Pfizer: Consultancy; Sunesis: Consultancy; Daiichi Sankyo: Consultancy; Pfizer: Consultancy; Ariad: Consultancy; Daiichi Sankyo: Consultancy; GlycoMimetics: Other: Data Safety and Monitoring Committees; Ariad: Consultancy; Jannsen (J & J): Other: Data Safety and Monitoring Committees ; GlycoMimetics: Other: Data Safety and Monitoring Committees; Jannsen (J & J): Other: Data Safety and Monitoring Committees. Savona:Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding. Warsi:Novartis Pharmaceutical Corporation: Employment. Paley:Novartis Oncology: Employment. Dautaj:Novartis Pharmaceutical Corporation: Employment. Lin:Novartis: Employment. Mauro:Ariad: Consultancy; Bristol-Myers Squibb: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.4050.4050

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. 140, No. Supplement 1 ( 2022-11-15), p. 9057-9060

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-169307

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

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. 522-522

Abstract: Acknowledgements: This work was funded by the following NIH/NCI/NCTN grant awards: RO1CA190661, R01CA160872, U10CA180888, U10CA180819, U24CA196175. The authors wish to gratefully acknowledge the importantcontributions of the late Dr. Stephen H. Petersdorf to SWOG and to the study S0106. The authors would like to acknowledge that a portion of the specimens were obtained from the Fred Hutch/University of Washington Hematopoietic Disorder Repository. AML is a molecularly heterogenous disease that harbors multiple genomic, epigenomic, and transcriptomic abnormalities. Despite the use of newer therapeutic agents and identification of multiple prognostic markers, most patients with AML still relapse or succumb to their disease. Understanding biological factors that determine relapse is of major clinical interest in AML. Proteins are responsible for much of the functional biology of the cells. However, few studies have examined the global proteome in AML, and, to our knowledge, studies have not previously examined the proteome in highly enriched undifferentiated AML blasts. Therefore, we have developed an integrated approach utilizing mass spectrometry-based proteomics and leveraging next generation RNA sequencing (RNAseq) to identify novel protein biomarkers associated with clinical outcome in a homogeneous population of undifferentiated viable leukemic blasts (uVLBs) from AML patients. Cryopreserved specimens from previously untreated de novo AML patients (n=27) were obtained from the SWOG Leukemia Repository. Patients were treated with dose intensive induction and consolidation as part of SWOG-9031, SWOG-9333, S0106, and S0112 studies. uVLBs were isolated from specimens using fluorescence-activated cell sorting (FACS). Targeted genome sequencing examined for genomic mutations in uVLBs, while global RNA sequencing (RNAseq) and tandem mass tag labelling followed by liquid chromatograph with tandem mass spectrometry (TMT-LC-MS/MS) were used to quantify transcript and protein expression, respectively. Analyses identified 6761 unique proteins, with 238 and 460 proteins significantly associated with complete response (CR) and overall survival (OS), respectively. There was modest overlap between the prognostically significant transcript and protein biomarkers (Figure 1). We also were able to identify and quantify aberrant proteins arising from genomic mutations . Examples of the "neoproteins" detected included proteins harboring NPM1 mutations (Figure 2a) and those harboring frameshift insertions/deletions in the terminal region of RUNX1 (Figure 2b). For validation of prognostic associations, we examined the proteome in an independent population of de novo AML patients (N=27) treated at the Fred Hutch and University of Washington. As with the SWOG patients, pre-treatment specimens were obtained from patients receiving intensive induction and consolidation with curative intent; however, OS data was not available for many of these patients. As such, the validation studies focused on CR. Patients were randomized by CR response into 9 pools (CR=6 and no CR=3 pools), and specimens were sorted for uVLBs. TMT-based LC-MS/MS quantified protein expression across pools, and analyses examined the prognostic significance of the 238 proteins from the SWOG analyses associated with CR. Thirteen of the most promising candidates were significantly associated with CR prognosis (Table 1), many of which are associated with cancer biology. Together, these studies show the feasibility and biological importance of examining the proteome in uVLBs. Studies examining for biomarkers in the proteome may be a powerful tool to uncover novel prognostic biomarkers that would otherwise not be identified by examining the genome or transcriptome. Furthermore, the multi-omics approach can be used to confirm the translation of potential neoantigens into actionable protein targets, which may lead to more cost-effective mechanisms for the development of innovative adoptive immunotherapies. Figure 1 Figure 1. Disclosures Othus: Biosight: Consultancy; Merck: Consultancy; Celgene: Other: Data safety monitoring board; Glycomimetics: Other: Data safety monitoring board; Daiichi Sankyo: Consultancy. Moseley: BioSight Ltd: Consultancy. Erba: AbbVie Inc; Agios Pharmaceuticals Inc; Bristol Myers Squibb; Celgene, a Bristol Myers Squibb company; Incyte Corporation; Jazz Pharmaceuticals Inc; Novartis: Speakers Bureau; AbbVie Inc; Agios Pharmaceuticals Inc; Astellas; Bristol Myers Squibb; Celgene, a Bristol Myers Squibb company; Daiichi Sankyo Inc; Genentech, a member of the Roche Group; GlycoMimetics Inc; Incyte Corporation; Jazz Pharmaceuticals Inc; Kura Oncology; Nov: Other: Advisory Committee; AbbVie Inc: Other: Independent review committee; AbbVie Inc; Agios Pharmaceuticals Inc; ALX Oncology; Amgen Inc; Daiichi Sankyo Inc; FORMA Therapeutics; Forty Seven Inc; Gilead Sciences Inc; GlycoMimetics Inc; ImmunoGen Inc; Jazz Pharmaceuticals Inc; MacroGenics Inc; Novartis; PTC Therapeutics: Research Funding. Radich: Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-151246

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

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detail.hit.zdb_id: 80069-7