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    Natalia Neparidze, MD

    Associate Professor of Internal Medicine (Hematology)
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    Additional Titles

    Research Leader, Myeloma Program, Hematology

    About

    Titles

    Associate Professor of Internal Medicine (Hematology)

    Research Leader, Myeloma Program, Hematology

    Biography

    Dr. Neparidze obtained her medical degree from Aieti Medical School in Tbilisi, Georgia in 2000. She subsequently completed Postdoctoral Research Fellowships at Emory, Northwestern and Yale Universities, followed by Internal Medicine Residency and Hematology/Medical Oncology Fellowship at Yale University. She has served as an assistant professor at Yale University School of Medicine, Medical Oncology/Hematology since 2012.  She specializes in multiple myeloma, monoclonal gammopathies, AL amyloidosis, Waldenstrom's macroglobulinemia. 

    Dr. Neparidze has developed multiple research projects in myeloma, including a number of investigator-initiated therapeutic clinical trials. She collaborates with other researchers nationally and internationally, serve as a PI and co-PI on multiple therapeutic clinical trials and leads several clinical outcomes studies in patients with myeloma.

    She serves as the leader of the Yale Myeloma Research team. 

    Her ongoing research directions include use of advanced imaging and evaluating tumor heterogeneity to enhance precision medicine approaches for myeloma, novel combination immunotherapy strategies and MRD-driven therapies in myeloma, as well as studying biology and clinical outcomes of monoclonal gammopathies in association with metabolic, viral and other co-morbidities, investigating mechanisms of tumor progression and resistance in myeloma.

    Dr. Neparidze is actively involved in educational process, teaching Hematology/Oncology fellows, medical students, residents and colleagues at Yale and in community.

    Learn more about Dr. Neparidze>>

    Appointments

    • Hematology

      Associate Professor on Term
      Primary

    Other Departments & Organizations

    Education & Training

    Fellowship
    Yale University (2010)
    Residency
    Hospital of St Raphael, New Haven, CT (2007)
    Post Doctoral Research Associate
    Yale University (2004)
    MD
    Aieti Medical School (2000)

    Research

    Overview

    My ongoing research direction includes incorporation and systematic use of advanced imaging with whole

    body MRI in myeloma response assessment, and targeted biopsies of myeloma lesions to study tumor

    heterogeneity, evaluate and compare genomic and transcriptome profile of focal lesions. As a result of my

    collaboration with Yale Musculoskeletal Radiology, I developed and completed clinical trial (IIT) titled “Global

    Response Assessment by Advanced Imaging and Lesion Biopsies During Induction Therapy of Multiple

    Myeloma“ during 2018-2021. As part of a correlative project, we developed imaging scoring system evaluating

    myeloma lesions by whole-body MRI and studying spatial heterogeneity of myeloma lesions.

    Neparidze, N. Whole body magnetic resonance imaging in newly diagnosed multiple myeloma: Influence

    on treatment decisions. J Blood Disord Transfus. 2017 DOI: 10.4172/2155-9864-C1-022



     I led the large-scale outcomes study utilizing Flatiron Myeloma cohort to examine the overall survival and

    outcomes of patients with myeloma harboring chromosome 1 cytogenetic abnormalities (C1As). We

    demonstrated that in this large cohort of patients with myeloma (N=3578) median OS was lower for patients

    with C1As (46.6 vs 70.1 months). C1As were independently associated with worse OS, as were older age, 

    higher R-ISS stage, high-risk cytogenetic abnormalities, and immunoglobulin A isotype. C1As were associated

    with inferior OS, independent of other high-risk cytogenetics, and despite greater use of novel therapies. We

    concluded that clinical trials testing newer therapies for high-risk MM should incorporate patients with C1As.

    Giri, S, and Neparidze, N et al. Chromosome 1 abnormalities and survival of patients with multiple myeloma in

    the era of novel agents. Blood Adv 2020 May 26;4(10):2245-2253. doi: 10.1182/bloodadvances.2019001425.

    My collaboration with Flatiron has led to another important outcomes study published in Leukemia examining

    the impact of early COVID-19 pandemic in which we demonstrated that reasonable care continued for patients

    with myeloma in the US despite challenges posed by the pandemic.

    Neparidze N, Wang R, Zeidan AM, Podoltsev NA, Shallis RM, Ma X, Davidoff AJ, Huntington SF.Changes in

    multiple myeloma treatment patterns during the early COVID-19 pandemic period.Leukemia. 2022 Jun 27;. doi:

    10.1038/s41375-022-01633-x. [Epub ahead of print] PubMed PMID: 35761025.

    Recent / ongoing research:

    Agency: Yale Cancer Center, Janssen

    Title: IIS. Prospective, Observational Study of Real-world Efficacy and Quality of Life Outcomes with

    Daratumumab Regimens in Relapsed MM

    PI: Natalia Neparidze, MD

    Aim: This investigator-initiated, multicenter, clinical research study is aimed to evaluate a real-world efficacy

    and patient-reported health-related quality of life outcomes in an observational prospective manner.

    Agency: Flatiron and Yale COPPER / School of Public Health

    ID YCC/COPPER

    PI: Natalia Neparidze, MD

    Title: Chromosome 1 Abnormalities and Clinical Outcomes in Multiple Myeloma in the Era of Novel Agents

    This study evaluated clinical outcomes in patients with multiple myeloma and Chromosome 1 aberrations

    utilizing Flatiron multiple myeloma cohort of over 8000 patients.

    Agency: DeLuca Foundation

    PI: Natalia Neparidze, MD

    Title: Evaluation of Clonal Heterogeneity and Therapeutic Targets in Multiple Myeloma.

    Aim: This study evaluated myeloma clonal spatial heterogeneity by comparing genome abnormalities between

    bone marrow and myeloma lesions to identify actionable targets for treatment.

    Agency: GlaxoSmithKline.

    PI: Natalia Neparidze, MD

    Title of IIS: Novel Combination of Belantamab Mafodotin and Elotuzumab to Enhance Therapeutic Efficacy in

    Multiple Myeloma.

    This study evaluates the novel immunotherapy combination with antibody-drug conjugate Belantamab

    Mafodotin plus a checkpoint inhibitor elotuzumab in patients with relapsed/refractory myeloma.

    “Clinical regressions and broad immune activation following combination therapy targeting human NKT cells in myeloma” is my earliest significant published work. I was involved as this translational research study was designed and launched at Yale University. I was subsequently involved in screening, enrolling and treating the patients on this phase I/II trial. Natural killer T cells can help mediate immune surveillance against tumors. They play an important role as orchestrators of immune system in multiple myeloma. Clinical myeloma is preceded by an asymptomatic precursor phase. 

    We treated patients with asymptomatic myeloma with combination of lipid α-galactosylceramide-loaded dendritic

    cells and low-dose lenalidomide. The treatment was well tolerated and resulted in clinical responses. Clinical

    responses correlated with treatment-induced antitumor T-cell immunity. Broad changes in the repertoire of NKT

    cells, activation of monocyte/macrophage system and eosinophils was observed. These data demonstrated

    synergistic activation of several innate immune cells by this combination and the capacity to mediate tumor

    regression. The study provided an important, first-in-human experience with targeting lipid reactive T cells in

    combination with lenalidomide in myeloma. This was an important proof-of concept study demonstrating that

    combination therapies targeting NKT cells may be of benefit toward prevention of cancer in humans. Additionally,

    the study greatly enhanced our understanding of subsets of lipid-reactive NKT cells, which paved the wave for

    further seminal work on lipid antigens in the origins of myeloma by our group.

    Neparidze, N and Dhodapkar, MV. Understanding the role of Natural Killer T (NKT) cells in

    hematologic malignancies: progress and challenges. Chapter. Natural Killer T Cells. Cancer Drug

    Discovery and Development 2012, pp 153-167

    J. Richter, N. Neparidze, L. Zhang, S. Nair, T. Monesmith, R. Sundaram, F. Miesowicz, K. M.

    Dhodapkar, and M. V. Dhodapkar. Clinical regressions and broad immune activation following

    combination therapy targeting human NKT cells in myeloma. Plenary Paper. Blood -2013 121:423-430

    At the VA CT Cancer Center I evaluated the efficiency, clinical outcomes and patient /provider satisfaction of

    newly implemented electronic hematology consults at VACT. We concluded that in an integrated health care

    system with a comprehensive EMR, e-consults offer a timely and patient-centered option for providing

    hematology specialist input for select patients. Further studies are necessary to determine the role this method

    of delivering hematologic care and its effect on our health care system, how virtual care workload should be

    compensated, its impact on the workload of hematologists, and the quality of care delivered.

    Cecchini M, Rose MG, Wong EY, and Neparidze N. The implementation of electronic hematology consults

    at a VA Hospital. Blood. 2016 Jan 2509-672113


    While serving at VA CT Cancer Center, I developed a protocol under the auspices of VACS – Veterans Aging

    Cohort Study, with the aim to evaluate biology and clinical outcomes of multiple myeloma in association with HIV

    infection. Analysis of the data from the VACS cohorts of HIV-infected and HIV-uninfected veterans with multiple

    myeloma is ongoing to compare clinical, morphologic and genomic features of HIV-associated myeloma. This

    study is expected to provide significant insights into disease biology, outcomes and treatment of patients with

    myeloma and HIV infection.

    Impact of HIV on Clinical Presentation and Outcomes of Individuals with Multiple Myeloma.

    Smith Giri, Ellice Y. Wong, Michal Rose, Roxanne Wadia, Lesley S. Park, Amy

    Justice and Natalia Neparidze Blood 2018 132:3162; doi: https://doi.org/10.1182/blood-...

    Medical Research Interests

    Amyloidosis; Hematology; Leukemia, Plasma Cell; Multiple Myeloma; Myeloma Proteins; Neoplasms, Plasma Cell; Paraproteinemias; Smoldering Multiple Myeloma; Waldenstrom Macroglobulinemia

    Research at a Glance

    Yale Co-Authors

    Frequent collaborators of Natalia Neparidze's published research.

    Publications

    Featured Publications

    2024

    Clinical Trials

    Academic Achievements & Community Involvement

    • activity

      Monoclonal Antibodies and Adverse Event Profile in Multiple Myeloma

    • activity

      Development of New Scoring System for Whole Body Magnetic Resonance Imaging for Evaluation of Multiple Myeloma Lesions

    Clinical Care

    Overview

    Clinical Specialties

    Hematologic Oncology; Hematology

    Fact Sheets

    Board Certifications

    • Medical Oncology

      Certification Organization
      AB of Internal Medicine
      Latest Certification Date
      2020
      Original Certification Date
      2010
    • Hematology (Internal Medicine)

      Certification Organization
      AB of Internal Medicine
      Latest Certification Date
      2020
      Original Certification Date
      2010

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