Evidence map›Paper›PMID 36593070›Full record

ArticleJournal for immunotherapy of cancer2023

Modulation of myeloid and T cells in vivo by Bruton's tyrosine kinase inhibitor ibrutinib in patients with metastatic pancreatic ductal adenocarcinoma.

Meenal Sinha, Courtney Betts, Li Zhang, Madeline J Griffith, Isabelle Solman, Brandon Chen, Eric Liu, Whitney Tamaki, Jacob Stultz, Jaqueline Marquez and 19 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02562898 (A Study of the Safety, Immunopharmacodynamics and Anti-tumor Activity of Ibrutinib Combined With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Adenocarcinoma), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.1field-weighted citation impact, top 12% 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.

NCT02562898 phase1 / phase2completednot on this map

A Study of the Safety, Immunopharmacodynamics and Anti-tumor Activity of Ibrutinib Combined With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Adenocarcinoma

TypeinterventionalSponsorMargaret TemperoRan2015 to 2020Enrolled18ConditionsMetastatic Pancreatic AdenocarcinomaArmsIbrutinib, Paclitaxel, Gemcitabine
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
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

29 authors at 4 institutions in 1 country.

Meenal SinhaDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA.ORCID 0000-0002-4008-4080
Courtney BettsDepartment of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, USA.
Li ZhangDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA.
Madeline J GriffithDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA.
Isabelle SolmanAbbVie, Irvine, California, USA.
Brandon ChenDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA.
Eric LiuDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA.ORCID 0000-0003-2286-0856
Whitney TamakiDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA.
Jacob StultzDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA.
Jaqueline MarquezDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA.
Shamilene SivagnanamDepartment of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, USA.
Alexander CheungDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA.ORCID 0000-0002-2115-6966
Denise PenerDepartment of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Anne FahlmanDepartment of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Erin TaberDepartment of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Kimberly LernerDepartment of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Matthew CrockerDepartment of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Kendra ToddDepartment of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Brindha RajagopalanDepartment of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Clarisha WareDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA.
Mark BridgeDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA.
Johnson VoDepartment of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Hannah DragomanovichDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA.
Julie Sudduth-KlingerDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA.
Gina VaccaroMedical Oncology, Providence Portland Medical Center, Portland, Oregon, USA.
Charles D LopezDepartment of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, USA.
Margaret TemperoDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA.
Lisa M Coussens *Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon, USA.
Lawrence Fong *Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, California, USA lawrence.fong@ucsf.edu.
University of California, San Francisco · USOregon Health & Science University · USAbbVie (United States) · USProvidence Portland Medical Center · US

Funding

Determinants of response to cancer immunotherapyR35CA253175 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Lawrence Fong · 2021 to 2026
$5.8M
Computational approaches to unravel immune receptor sequencing for cancer immunotherapyR21CA264381 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ZHANG, LI · 2021 to 2022
$384k
NCI NIH HHS R21 CA264381NCI NIH HHS R35 CA253175
6 · The paper itself

Abstract

backgroundIn preclinical studies of pancreatic ductal adenocarcinoma (PDAC), ibrutinib improved the antitumor efficacy of the standard of care chemotherapy. This led to a phase 1b clinical trial to determine the safety, tolerability, and immunologic effects of ibrutinib treatment in patients with advanced PDAC.

methodsPreviously untreated patients with PDAC were enrolled in a phase 1b clinical trial (ClinicalTrials.gov) to determine the safety, toxicity, and maximal tolerated dose of ibrutinib when administered with the standard regimen of gemcitabine and nab-paclitaxel. To study the immune response to ibrutinib alone, the trial included an immune response arm where patients were administered with ibrutinib daily for a week followed by ibrutinib combined with gemcitabine and nab-paclitaxel. Endoscopic ultrasonography-guided primary PDAC tumor biopsies and blood were collected before and after ibrutinib monotherapy. Changes in abundance and functional state of immune cells in the blood was evaluated by mass cytometry by time of flight and statistical scaffold analysis, while that in the local tumor microenvironment (TME) were assessed by multiplex immunohistochemistry. Changes in B-cell receptor and T-cell receptor repertoire were assessed by sequencing and analysis of clonality.

resultsIn the blood, ibrutinib monotherapy significantly increased the frequencies of activated inducible T cell costimulator

conclusionIbrutinib monotherapy skewed the immune landscape both in the circulation and TME towards activated T cells, monocytes and DCs. These effects were not observed when combining ibrutinib with standard of care chemotherapy. Future studies may focus on other therapeutic combinations that augment the immunomodulatory effects of ibrutinib in solid tumors. TRIAL REGISTRATION NUMBER: NCT02562898.

Indexed as

AdenocarcinomaAntineoplastic AgentsCarcinoma, Pancreatic DuctalPancreatic NeoplasmsAdenineGemcitabineHumansPiperidinesProgrammed Cell Death 1 ReceptorTumor MicroenvironmentTyrosine Kinase InhibitorsAdenineAntineoplastic AgentsGemcitabineibrutinibPiperidinesProgrammed Cell Death 1 ReceptorTyrosine Kinase InhibitorsImmunomodulationImmunotherapyLymphocyte ActivationReceptors, ImmunologicTumor Microenvironment

Identifiers

PMID36593070
PMCPMC9809229
OpenAlexW4313406776

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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 OpenQuestion graph.