Evidence map›Paper›PMID 34496014›Full record

Trial reportBlood2022

Pembrolizumab for B-cell lymphomas relapsing after or refractory to CD19-directed CAR T-cell therapy.

Elise A Chong, Cécile Alanio, Jakub Svoboda, Sunita D Nasta, Daniel J Landsburg, Simon F Lacey, Marco Ruella, Siddharth Bhattacharyya, E John Wherry, Stephen J Schuster

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase II
In one paragraph

Trial report in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02650999 (Phase I/II Study of Pembrolizumab in Patients Failing to Respond to or Relapsing After Anti-CD19 Chimeric Antigen Receptor Modified T Cell Therapy for Relapsed or Refractory CD19+ Lymphomas), which is not on this map. Cited by 141 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
141citing papers in PubMed, 3 pooled it
11.4field-weighted citation impact, top 1% 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.

NCT02650999 phase1 / phase2completednot on this map

Phase I/II Study of Pembrolizumab in Patients Failing to Respond to or Relapsing After Anti-CD19 Chimeric Antigen Receptor Modified T Cell Therapy for Relapsed or Refractory CD19+ Lymphomas

TypeinterventionalSponsorAbramson Cancer Center at Penn MedicineRan2016 to 2020Enrolled12ConditionsCD19+ Diffuse Large B-cell Lymphomas, Follicular Lymphomas, Mantle Cell LymphomasArmsPembrolizumab
3 · Its place in the literature

Who cites it

141 citing papers in PubMed, 3 syntheses or guidelines pooled it, 181 citations in OpenAlex.

  1. Pooled it
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  13. Neurological complications of current and emerging CAR-T cell therapies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
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81 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Elise A ChongLymphoma Program, Abramson Cancer Center.ORCID 0000-0001-8895-1625
Cécile AlanioInstitute for Immunology, and.ORCID 0000-0003-2785-7445
Jakub SvobodaLymphoma Program, Abramson Cancer Center.
Sunita D NastaLymphoma Program, Abramson Cancer Center.
Daniel J LandsburgLymphoma Program, Abramson Cancer Center.
Simon F LaceyCenter for Cellular Immunotherapies, and.
Marco RuellaLymphoma Program, Abramson Cancer Center.ORCID 0000-0003-4301-5811
Siddharth BhattacharyyaDepartment of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA.
E John WherryInstitute for Immunology, and.ORCID 0000-0003-0477-1956
Stephen J SchusterLymphoma Program, Abramson Cancer Center.ORCID 0000-0002-3376-8978
Abramson Cancer CenterParker Institute for Cancer Immunotherapy · USUniversity of Pennsylvania · US

Funding

Virology CoreU19AI082630 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG, GEORG Michael LAUER · 2009 to 2026
$48.1M
Project 3: Combinatorial and gene-editing approaches to enhance the efficacy of CAR T cell therapy of multiple myeloma.P01CA214278 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Joseph Anthony Fraietta · 2017 to 2026
$26.8M
Sequencing and Viral Evolution CoreU19AI117950 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WHERRY, E. JOHN · 2015 to 2019
$12.0M
Radiation and checkpoint blockade for cancer immune therapyP01CA210944 · NCI · UNIVERSITY OF PENNSYLVANIA · PI WHERRY, E. JOHN · 2017 to 2022
$11.5M
CANCER RESEARCH TRAINING PROGRAMT32CA009615 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Gregory L Beatty, MICHAEL D HOGARTY · 1988 to 2026
$10.4M
Temporal control of differentiation and epigenetics of Exhausted CD8 T cells by ToxR01AI155577 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WHERRY, E. JOHN · 2020 to 2024
$2.7M
MODULATION OF CD5 SIGNALING TO ENHANCE ADOPTIVE T-CELL THERAPIES FOR CANCERR37CA262362 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Marco Ruella · 2022 to 2026
$2.6M
Resistance To Targeted Immunotherapies:CART19 as a ParadigmR00CA212302 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RUELLA, MARCO · 2018 to 2020
$608k
Resistance To Targeted Immunotherapies:CART19 as a ParadigmK99CA212302 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RUELLA, MARCO · 2017 to 2018
$348k
NCI NIH HHS K99 CA212302NCI NIH HHS P01 CA210944NCI NIH HHS P01 CA214278NCI NIH HHS R00 CA212302NCI NIH HHS T32 CA009615NIAID NIH HHS R01 AI155577NIAID NIH HHS U19 AI082630NIAID NIH HHS U19 AI117950
6 · The paper itself

Abstract

CD19-directed chimeric antigen receptor-modified (CAR T) T cells achieve durable remissions in about 30% to 40% of relapsed/refractory large B-cell lymphomas. T-cell exhaustion and/or an immunosuppressive tumor microenvironment may contribute to CAR T-cell failure. Pembrolizumab, an anti-PD1 immune checkpoint inhibitor, may reverse T-cell exhaustion after CAR T-cell therapy. We treated 12 patients with B-cell lymphomas who were either refractory to (n = 9) or relapsed after (n = 3) CD19-directed CAR T-cell (4-1BB-costimulated) therapy with pembrolizumab 200 mg IV every 3 weeks. Median time from CAR T-cell infusion to first pembrolizumab dose was 3.3 months (range, 0.4-42.8 months). Pembrolizumab was well tolerated, and the only grade ≥3 adverse events related to pembrolizumab were neutropenia (n = 3; 25%). Best overall response rate after pembrolizumab was 25% (3 of 12 patients; 1 complete response; 2 partial responses). One (8%) patient had stable disease; thus, 4 of 12 (33%) patients had clinical benefit. After pembrolizumab, 4 patients with clinical benefit had an increase in percentage of CAR T cells by mass cytometry by time of flight (CyTOF); 3 of 4 of these patients also had increases in CAR19 transgene levels by quantitative polymerase chain reaction. Deep immune profiling using CyTOF revealed increased CAR T-cell activation and proliferation and less T-cell exhaustion in clinical responders. Together, PD1 blockade with pembrolizumab after CD19-directed CAR T-cell therapy appears safe and may achieve clinical responses in some patients with B-cell lymphomas refractory to or relapsed after CAR T-cell therapy. This trial was registered at www.clinicaltrials.gove as #NCT02650999.

Indexed as

Salvage TherapyAdultAgedAntibodies, Monoclonal, HumanizedAntigens, CD19Antineoplastic Agents, ImmunologicalFemaleFollow-Up StudiesHumansImmunotherapy, AdoptiveLymphoma, B-CellMaleMiddle AgedNeoplasm Recurrence, LocalPrognosisProspective StudiesAntibodies, Monoclonal, HumanizedAntigens, CD19Antineoplastic Agents, ImmunologicalpembrolizumabReceptors, Chimeric Antigen

Identifiers

PMID34496014
PMCPMC9211527
OpenAlexW3198679689

What OpenQuestion holds

Textmetadata
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.