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INFORMATION FOR

Natalia Neparidze, MD

Associate Professor of Internal Medicine (Hematology); Research Leader, Myeloma Program, Hematology

Research Summary

Developmental therapeutics, designing clinical trials in multiple myeloma, with specific interests in advanced imaging, tumor heterogeneity and tumor resistance in myeloma, strategies for advancing maintenance therapy, and eradication of minimal residual disease in multiple myeloma.

Extensive Research Description

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-...

Coauthors

Research Interests

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

Selected Publications

  • Second Malignancies Among Older Patients with Classical Myeloproliferative Neoplasms Treated with RuxolitinibStempel J, Wang R, Shallis R, Huntington S, Zeidan A, Neparidze N, Di M, Ma X, Podoltsev N. Second Malignancies Among Older Patients with Classical Myeloproliferative Neoplasms Treated with Ruxolitinib Blood 2022, 140: 11004-11006. DOI: 10.1182/blood-2022-165156.
  • Genomic Sequencing of Paired Bone Marrow and Focal Lesion Biopsies of Newly Diagnosed Multiple Myeloma Patients before and after Induction TherapyLiu Y, Browning S, VanOudenhove J, Biancon G, Bar N, Parker T, Anderson T, Dhodapkar M, Seropian S, Halene S, Xu M, Gorshein E, Talsania A, Kidwai W, Witt D, Chang V, Montanari F, Lischuk A, Haims A, Wei W, Neparidze N. Genomic Sequencing of Paired Bone Marrow and Focal Lesion Biopsies of Newly Diagnosed Multiple Myeloma Patients before and after Induction Therapy Blood 2022, 140: 7086-7087. DOI: 10.1182/blood-2022-168109.
  • Outcomes Among Primary Refractory Multiple Myeloma Patients in the Era of Monoclonal Antibodies: The Yale ExperienceLiu Y, Kywe B, Crawford L, Lora F, Bar N, Browning S, Gorshein E, Parker T, Neparidze N. Outcomes Among Primary Refractory Multiple Myeloma Patients in the Era of Monoclonal Antibodies: The Yale Experience Blood 2021, 138: 1635-1635. DOI: 10.1182/blood-2021-146619.
  • Evaluation of International Working Group 2006 Response Criteria in Patients with Higher-Risk Myelodysplastic Syndromes (HR-MDS) Treated with Hypomethylating Agent Monotherapy in the Frontline SettingBewersdorf J, Wei W, Jaiani A, Patel P, Mehta R, Neparidze N, Shallis R, Podoltsev N, Brunner A, Zeidan A. Evaluation of International Working Group 2006 Response Criteria in Patients with Higher-Risk Myelodysplastic Syndromes (HR-MDS) Treated with Hypomethylating Agent Monotherapy in the Frontline Setting Blood 2021, 138: 3701-3701. DOI: 10.1182/blood-2021-146331.
  • Survival of Mantle Cell Lymphoma in the Era of Bruton Tyrosine Kinase Inhibitors: A Population-Based AnalysisDi M, Cui C, Kothari S, Zeidan A, Podoltsev N, Neparidze N, Shallis R, Wang R, Ma X, Huntington S. Survival of Mantle Cell Lymphoma in the Era of Bruton Tyrosine Kinase Inhibitors: A Population-Based Analysis Blood 2021, 138: 182-182. DOI: 10.1182/blood-2021-146417.
  • Contemporary "Real World" Molecular Testing and Tyrosine Kinase Inhibitor Adherence Patterns Among Older Pts with Chronic Myeloid Leukemia in the United StatesShallis R, Wang R, Zeidan A, Huntington S, Neparidze N, Di M, Ma X, Podoltsev N. Contemporary "Real World" Molecular Testing and Tyrosine Kinase Inhibitor Adherence Patterns Among Older Pts with Chronic Myeloid Leukemia in the United States Blood 2021, 138: 282-282. DOI: 10.1182/blood-2021-151066.
  • Racial and Age-Related Differences in Impacts of High-Risk Cytogenetic Abnormalities on Survival in Multiple Myeloma in a Nationwide Electronic Health Record-Derived DatabaseCalip G, Ascha M, Wang X, Pierre A, Maignan K, Wadé N, Leng S, Seymour E, Chiu B, Sweiss K, Patel P, Neparidze N. Racial and Age-Related Differences in Impacts of High-Risk Cytogenetic Abnormalities on Survival in Multiple Myeloma in a Nationwide Electronic Health Record-Derived Database Blood 2021, 138: 4121-4121. DOI: 10.1182/blood-2021-152774.
  • Racial Disparities in Telemedicine Uptake during the COVID-19 Pandemic Among Patients with Hematologic Malignancies in the United StatesNeparidze N, Lau K, Wang X, Davidoff A, Huntington S, Jamy O, Calip G, Shah H, Stephens D, Miksad R, Parikh R, Takvorian S, Goyal G, Seymour E. Racial Disparities in Telemedicine Uptake during the COVID-19 Pandemic Among Patients with Hematologic Malignancies in the United States Blood 2021, 138: 1973-1973. PMCID: PMC8701527, DOI: 10.1182/blood-2021-153787.
  • Advanced Imaging and Targeted Myeloma Lesion Biopsies to Enhance Global Response Assessment and Evaluate Spatial Heterogeneity in Multiple MyelomaBrowning S, Parker T, Bar N, Anderson T, Dhodapkar M, Seropian S, Lee A, Prebet T, Halene S, Xu M, Gorshein E, Talsania A, Kidwai W, Witt D, Chang V, Lischuk A, Wei W, Haims A, Neparidze N. Advanced Imaging and Targeted Myeloma Lesion Biopsies to Enhance Global Response Assessment and Evaluate Spatial Heterogeneity in Multiple Myeloma Blood 2020, 136: 20-22. DOI: 10.1182/blood-2020-136478.
  • Oncologist Sub-Specialization, Care Setting, and Multiple Myeloma Treatment and OutcomesDavidoff A, Long J, Neparidze N, Bewersdorf J, Shallis R, Podoltsev N, Wang R, Gore S, Zeidan A, Huntington S. Oncologist Sub-Specialization, Care Setting, and Multiple Myeloma Treatment and Outcomes Blood 2020, 136: 2-3. DOI: 10.1182/blood-2020-140728.
  • Clinical Outcomes of Patients (pts) with TP53-Mutated Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS): A Single Center ExperienceBewersdorf J, Shallis R, Gowda L, Hager K, Podoltsev N, Gore S, Prebet T, Halene S, Isufi I, Foss F, Huntington S, Kim T, Pillai M, Parker T, Neparidze N, Bar N, Seropian S, Siddon A, Zeidan A. Clinical Outcomes of Patients (pts) with TP53-Mutated Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS): A Single Center Experience Blood 2019, 134: 5173-5173. DOI: 10.1182/blood-2019-127162.
  • Isolated Trisomy 11 in Patients with Myeloid Malignancies - Is the Prognosis Not As Grim As Previously Thought?Bewersdorf J, Shallis R, Diadamo A, Gowda L, Podoltsev N, Gore S, Prebet T, Halene S, Isufi I, Foss F, Huntington S, Kim T, Pillai M, Parker T, Neparidze N, Bar N, Seropian S, Siddon A, Zeidan A. Isolated Trisomy 11 in Patients with Myeloid Malignancies - Is the Prognosis Not As Grim As Previously Thought? Blood 2019, 134: 5174-5174. DOI: 10.1182/blood-2019-127277.
  • Immune Checkpoint Inhibitor Therapy for Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndromes: A Single-Center ExperienceShallis R, Bewersdorf J, Gowda L, Podoltsev N, Prebet T, Gore S, Halene S, Isufi I, Foss F, Huntington S, Kim T, Pillai M, Parker T, Neparidze N, Bar N, Seropian S, Zeidan A. Immune Checkpoint Inhibitor Therapy for Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndromes: A Single-Center Experience Blood 2019, 134: 1330-1330. DOI: 10.1182/blood-2019-127422.
  • Daratumumab in the Clinic, a Real-Word Experience at Yale Cancer CenterBrowning S, Parker T, Bar N, Seropian S, Lee A, Anderson T, Neparidze N. Daratumumab in the Clinic, a Real-Word Experience at Yale Cancer Center Blood 2019, 134: 5569-5569. DOI: 10.1182/blood-2019-130134.
  • Patterns of Care and Clinical Outcomes with 7+3 Induction Chemotherapy for Patients (pts) with Acute Myeloid Leukemia (AML) in the United States (US): A Large Population-Based StudyZeidan A, Podoltsev N, Wang X, Bewersdorf J, Shallis R, Huntington S, Neparidze N, Giri S, Gore S, Ma X, Davidoff A, Wang R. Patterns of Care and Clinical Outcomes with 7+3 Induction Chemotherapy for Patients (pts) with Acute Myeloid Leukemia (AML) in the United States (US): A Large Population-Based Study Blood 2019, 134: 116-116. DOI: 10.1182/blood-2019-126643.
  • Trial in Progress: Phase I Dose-Escalation and Dose-Expansion Trial of a Novel Glutaminase Inhibitor (CB-839 HCl) in Combination with Carfilzomib and Dexamethasone in Relapsed and/or Refractory Multiple MyelomaGonsalves W, Devarakonda S, Baz R, Neparidze N, Adjei A, Kunos C, Kumar S. Trial in Progress: Phase I Dose-Escalation and Dose-Expansion Trial of a Novel Glutaminase Inhibitor (CB-839 HCl) in Combination with Carfilzomib and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma Blood 2019, 134: 3160-3160. DOI: 10.1182/blood-2019-123399.
  • Chromosome 1 abnormalities and clinical outcomes in multiple myeloma in the era of novel agents.Giri S, Huntington S, Wang R, Zeidan A, Podoltsev N, Gore S, Ma X, Gross C, Davidoff A, Neparidze N. Chromosome 1 abnormalities and clinical outcomes in multiple myeloma in the era of novel agents. Journal Of Clinical Oncology 2019, 37: 8044-8044. DOI: 10.1200/jco.2019.37.15_suppl.8044.
  • Whole Exome Sequencing and Extended Thrombophilia Testing in Patients with Venous ThromboembolismShevell L, Lee E, Dhodapkar R, Dykas D, Popa A, Ma D, Bar N, Baluha A, Burns A, Ochoa Chaar C, Dupont A, Gu S, Halene S, Luciano R, Marien R, Neparidze N, Parker T, Yao X, Camire R, Ebberink E, Garcia de Frutos P, Gnanasambandan K, Sayeski P, Huntington J, Lentz S, Mertens K, Parish C, Rezaie R, Connors J, Leavitt A, Bale A, Lee A. Whole Exome Sequencing and Extended Thrombophilia Testing in Patients with Venous Thromboembolism Blood 2018, 132: 2506-2506. DOI: 10.1182/blood-2018-99-115529.
  • Atezolizumab in Combination with Daratumumab with or without Lenalidomide or Pomalidomide: A Phase Ib Study in Patients with Multiple MyelomaCho H, Costa L, Davies F, Neparidze N, Vij R, Feng Y, Teterina A, Wassner Fritsch E, Wenger M, Kaufman J. Atezolizumab in Combination with Daratumumab with or without Lenalidomide or Pomalidomide: A Phase Ib Study in Patients with Multiple Myeloma Blood 2018, 132: 597-597. DOI: 10.1182/blood-2018-99-114960.
  • Impact of HIV on Clinical Presentation and Outcomes of Individuals with Multiple MyelomaGiri S, Wong E, Rose M, Wadia R, Park L, Justice A, Neparidze N. Impact of HIV on Clinical Presentation and Outcomes of Individuals with Multiple Myeloma Blood 2018, 132: 3162-3162. DOI: 10.1182/blood-2018-99-115633.
  • Venous Thromboembolism (VTE) Education Preferences Amongst Physicians and Patients: A Qualitative Needs AssessmentJuthani P, Ahmed D, Ahmed O, Bona R, Neparidze N, Lee A. Venous Thromboembolism (VTE) Education Preferences Amongst Physicians and Patients: A Qualitative Needs Assessment Blood 2018, 132: 5810-5810. DOI: 10.1182/blood-2018-99-119418.
  • Efficient Engraftment and Disease Replication of Myelodysplastic Syndromes Using a Novel Humanized Mice ModelSong Y, Taylor A, Rongvaux A, Jiang T, Podoltsev N, Xu M, Neparidze N, Torres R, Barbarotta L, Balasubramanian K, Finberg K, Kluger Y, Flavell R, Halene S. Efficient Engraftment and Disease Replication of Myelodysplastic Syndromes Using a Novel Humanized Mice Model Blood 2015, 126: 4100-4100. DOI: 10.1182/blood.v126.23.4100.4100.
  • 26 HUMANIZED MICE AFFORD EFFICIENT ENGRAFTMENT AND DISEASE REPLICATION OF MYELODYSPLASTIC SYNDROMESSong Y, Rongvaux A, Taylor A, Podoltsev N, Xu M, Neparidze N, Torres R, Barbarotta L, Balasubramanian K, Finberg K, Flavell R, Halene S. 26 HUMANIZED MICE AFFORD EFFICIENT ENGRAFTMENT AND DISEASE REPLICATION OF MYELODYSPLASTIC SYNDROMES Leukemia Research 2015, 39: s11-s12. DOI: 10.1016/s0145-2126(15)30027-8.
  • Electronic Hematology Consultations at Veterans Affairs (VA) Connecticut: Analysis of Effects on Patient Care, and Provider and Patient SatisfactionNeparidze N, Cecchini M, Wong E, Rose M. Electronic Hematology Consultations at Veterans Affairs (VA) Connecticut: Analysis of Effects on Patient Care, and Provider and Patient Satisfaction Blood 2014, 124: 4857-4857. DOI: 10.1182/blood.v124.21.4857.4857.
  • Understanding the role of Natural Killer T (NKT) cells in hematologic malignancies: progress and challenges.Neparidze N and Dhodapkar, MV. Chapter. Natural Killer T Cells. Cancer Drug Discovery and Development 2012, pp 153-167
  • Understanding the Role of Natural Killer T Cells in Hematologic Malignancies: Progress and ChallengesNeparidze N, Dhodapkar M. Understanding the Role of Natural Killer T Cells in Hematologic Malignancies: Progress and Challenges 2011, 153-167. DOI: 10.1007/978-1-4614-0613-6_9.

Clinical Trials