Natalia Neparidze, MD

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-...