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  • 1
    In: Blood Advances, American Society of Hematology, Vol. 7, No. 12 ( 2023-06-27), p. 2733-2745
    Abstract: Venetoclax is an effective treatment for certain blood cancers, such as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). However, most patients relapse while on venetoclax and further treatment options are limited. Combining venetoclax with immunotherapies is an attractive approach; however, a detailed understanding of how venetoclax treatment impacts normal immune cells in patients is lacking. In this study, we performed deep profiling of peripheral blood (PB) cells from patients with CLL and AML before and after short-term treatment with venetoclax using mass cytometry (cytometry by time of flight) and found no impact on the concentrations of key T-cell subsets or their expression of checkpoint molecules. We also analyzed PB from patients with breast cancer receiving venetoclax long-term using a single-cell multiomics approach (cellular indexing of transcriptomes and epitopes by sequencing) and functional assays. We found significant depletion of B-cell populations with low expression of MCL-1 relative to other immune cells, attended by extensive transcriptomic changes. By contrast, there was less impact on circulating T cells and natural killer (NK) cells, with no changes in their subset composition, transcriptome, or function following venetoclax treatment. Our data indicate that venetoclax has minimal impact on circulating T or NK cells, supporting the rationale of combining this BH3 mimetic drug with cancer immunotherapies for more durable antitumor responses.
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2023
    detail.hit.zdb_id: 2876449-3
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  • 2
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 6010-6010
    Abstract: Background The growing number of treatment options for multiple myeloma has increased the complexity of clinical decision-making. Studies indicate significant variations in practice and adherence to treatment guidelines, but the root causes of this variability remain under-explored. We aimed to understand factors that influence clinician management strategies, and to assess potential differences in community vs. academic settings. Methods We conducted semi-structured qualitative interviews with physicians and non-physician clinicians in Southeastern U.S. academic (ACA) and community (COM) clinics. Interviews focused on contemporary management of multiple myeloma, guided by an expert panel of oncologists and qualitative researchers. De-identified audio files were transcribed, then coded and analyzed with NVivo 10 software, using an inductive and iterative constant comparative approach. Results Among the 20 participants, 13 were ACA and 7 were COM clinicians. We found marked variations between ACA and COM practice. All ACAs used formal risk stratification schema to inform treatment decisions, compared to just 1 COM clinician. COMs expressed uncertainty about how risk stratification models should impact practice, relying more on heuristic “rules of thumb.” COMs reported using a standardized basic set of treatment regimens across all myeloma patients; ACAs described a more nuanced, adaptive approach. COMs expressed frustration and difficulty keeping up with rapidly-evolving data from myeloma trials. In terms of transplant criteria, COMs placed more emphasis on psychosocial factors, and reported lower age cutoffs than ACA. Both ACA and COM clinicians noted challenges in determining timing of maintenance therapy initiation and in identifying relapse. Although physicians were the primary therapeutic decision-makers, non-physician clinicians influenced therapy selection and modification, and were often the first to detect toxicities. Conclusions Challenges to optimal management of multiple myeloma exist in both COM and ACA settings, including: the application of risk stratification and transplant eligibility criteria; the recognition of relapse and the timing of maintenance therapy initiation; and under-acknowledgement of the role of non-physician clinicians. Differences in reported practices between ACA vs. COM clinicians suggest opportunities for interventions to improve patient care and outcomes through optimal myeloma management and therapy selection. Disclosures LeBlanc: Celgene: Research Funding; Helsinn Therapeutics: Research Funding. Gasparetto:Celgene: Consultancy, Honoraria; Millenium: Honoraria. Tuchman:Celgene: Consultancy; Millenium: Consultancy, Research Funding; Novartis: Research Funding. Sheldon:Celgene: Research Funding. Howson:Celgene: Research Funding. Khan:Celgene: Employment, Equity Ownership, Leadership - Vice President Other. Kaura:Celgene: Employment, Equity Ownership. Abernethy:Genentech: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Research Funding; Celgene: Research Funding; Helsinn Therapeutics: Research Funding; Alexion Pharmaceuticals: Research Funding; Bristol-Myers Squibb: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; American Academy of Hospice and Palliative Medicine : President, President Other; Orange Leaf Associates: Employment; Advoset: Membership on an entity's Board of Directors or advisory committees; BioVex: Research Funding; DARA BioSciences: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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