Evidence map›Paper›PMID 37812476›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023

Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic Virus Therapy in a Phase Ib Trial.

Steffan T Nawrocki, Julian Olea, Claudia Villa Celi, Homa Dadrastoussi, Kaijin Wu, Denice Tsao-Wei, Anthony Colombo, Matt Coffey, Eduardo Fernandez Hernandez, Xuelian Chen and 8 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase I
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02514382 (A Phase 1b Study of REOLYSIN®), which is not on this map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02514382 phase1completednot on this map

A Phase 1b Study of REOLYSIN® (Reovirus Serotype 3 - Dearing Strain) Combined With Standard Doses of Bortezomib and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma

TypeinterventionalSponsorUniversity of Southern CaliforniaRan2015 to 2022Enrolled14ConditionsRecurrent Plasma Cell Myeloma, Refractory Plasma Cell MyelomaArmsBortezomib, Dexamethasone, Laboratory Biomarker Analysis, Pharmacological Study, Wild-type Reovirus
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. B4GALT5 inhibits CD8Journal for immunotherapy of cancer · 2025
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 7 institutions in 2 countries.

Steffan T Nawrocki *Division of Hematology and Oncology, Department of Medicine, University of Arizona Cancer Center, Tucson, Arizona.ORCID 0000-0001-8767-3969
Julian Olea *Division of Hematology, Health Sciences Campus, University of Southern California, Los Angeles, California.ORCID 0009-0008-9040-0804
Claudia Villa CeliDivision of Hematology, Health Sciences Campus, University of Southern California, Los Angeles, California.ORCID 0000-0001-6727-0505
Homa DadrastoussiDivision of Hematology, Health Sciences Campus, University of Southern California, Los Angeles, California.ORCID 0000-0002-5611-2883
Kaijin WuDivision of Hematology, Health Sciences Campus, University of Southern California, Los Angeles, California.ORCID 0009-0005-6604-5775
Denice Tsao-WeiDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.ORCID 0000-0003-2010-0829
Anthony ColomboDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.ORCID 0000-0002-4981-1651
Matt CoffeyOncolytics Biotech, Inc, Calgary, Alberta, Canada.ORCID 0000-0002-7211-829X
Eduardo Fernandez HernandezDivision of Hematology, Health Sciences Campus, University of Southern California, Los Angeles, California.ORCID 0000-0002-5489-5095
Xuelian ChenDivision of Hematology, Health Sciences Campus, University of Southern California, Los Angeles, California.ORCID 0000-0001-9051-0802
Gerard J NuovoThe Ohio State University Comprehensive Cancer Center Columbus, Columbus, Ohio.ORCID 0000-0002-5351-4721
Jennifer S CarewDivision of Hematology and Oncology, Department of Medicine, University of Arizona Cancer Center, Tucson, Arizona.ORCID 0000-0002-8578-8292
Ann F MohrbacherDivision of Hematology, Health Sciences Campus, University of Southern California, Los Angeles, California.ORCID 0009-0005-5823-5122
Paul FieldsFormerly, Adaptive Biotechnologies, Seattle, Washington; currently, Tempus Labs, Seattle, Washington.ORCID 0000-0002-9608-6464
Peter KuhnUSC Michelson Center for Convergent Biosciences and Department of Biological Sciences, University of Southern California, Los Angeles.ORCID 0000-0003-2629-4505
Imran SiddiqiDepartment of Pathology, University of Southern California, Los Angeles, California.ORCID 0000-0001-8083-9639
Akil MerchantSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.ORCID 0000-0001-7472-822X
Kevin R KellyDivision of Hematology, Health Sciences Campus, University of Southern California, Los Angeles, California.ORCID 0000-0002-3638-5956
University of Southern California · USUniversity of Arizona · USAdaptive Biotechnologies (United States) · USCedars-Sinai Medical Center · USConvergent Science (United States) · USOncolytics Biotech (Canada) · CAThe Ohio State University · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
Spatially resolved, single cell biomarkers of B cell lymphomaR01CA266544 · NCI · CEDARS-SINAI MEDICAL CENTER · PI Akil Merchant · 2022 to 2026
$3.2M
Endoplasmic reticulum stress and oncoviral therapyR01CA190789 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI NAWROCKI, STEFFAN T · 2015 to 2020
$1.6M
Development of lysosome targeted therapeuticsR41CA271967 · NCI · MAJESTIC THERAPEUTICS, LLC · PI CAREW, JENNIFER S, NAWROCKI, STEFFAN T · 2022 to 2022
$258k
NCI NIH HHS P30 CA014089NCI NIH HHS R01 CA190789NCI NIH HHS R01 CA266544NCI NIH HHS R41 CA271967
6 · The paper itself

Abstract

purposeOur preclinical studies showed that the oncolytic reovirus formulation pelareorep (PELA) has significant immunomodulatory anti-myeloma activity. We conducted an investigator-initiated clinical trial to evaluate PELA in combination with dexamethasone (Dex) and bortezomib (BZ) and define the tumor immune microenvironment (TiME) in patients with multiple myeloma treated with this regimen. PATIENTS AND

methodsPatients with relapsed/refractory multiple myeloma (n = 14) were enrolled in a phase Ib clinical trial (ClinicalTrials.gov: NCT02514382) of three escalating PELA doses administered on Days 1, 2, 8, 9, 15, and 16. Patients received 40 mg Dex and 1.5 mg/m2 BZ on Days 1, 8, and 15. Cycles were repeated every 28 days. Pre- and posttreatment bone marrow specimens (IHC, n = 9; imaging mass cytometry, n = 6) and peripheral blood samples were collected for analysis (flow cytometry, n = 5; T-cell receptor clonality, n = 7; cytokine assay, n = 7).

resultsPELA/BZ/Dex was well-tolerated in all patients. Treatment-emergent toxicities were transient, and no dose-limiting toxicities occurred. Six (55%) of 11 response-evaluable patients showed decreased paraprotein. Treatment increased T and natural killer cell activation, inflammatory cytokine release, and programmed death-ligand 1 expression in bone marrow. Compared with nonresponders, responders had higher reovirus protein levels, increased cytotoxic T-cell infiltration posttreatment, cytotoxic T cells in significantly closer proximity to multiple myeloma cells, and larger populations of a novel immune-primed multiple myeloma phenotype (CD138+ IDO1+HLA-ABCHigh), indicating immunomodulation.

conclusionsPELA/BZ/Dex is well-tolerated and associated with anti-multiple myeloma activity in a subset of responding patients, characterized by immune reprogramming and TiME changes, warranting further investigation of PELA as an immunomodulator.

Indexed as

Multiple MyelomaOncolytic VirotherapyAntineoplastic Combined Chemotherapy ProtocolsBortezomibCytokinesDexamethasoneHumansTumor MicroenvironmentBortezomibCytokinesDexamethasone

Identifiers

PMID37812476
PMCPMC10722139
OpenAlexW4387439283

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.