Evidence map›Paper›PMID 38996463›Full record

ArticleLancet (London, England)2024

CD22-directed CAR T-cell therapy for large B-cell lymphomas progressing after CD19-directed CAR T-cell therapy: a dose-finding phase 1 study.

Matthew J Frank, John H Baird, Anne Marijn Kramer, Hrishikesh K Srinagesh, Shabnum Patel, Annie Kathleen Brown, Jean S Oak, Sheren F Younes, Yasodha Natkunam, Mark P Hamilton and 11 more

2 registry-linked trialsAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Lancet (London, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
–field-weighted citation impact
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.

NCT04088890 phase1completednot on this map

Phase I/Ib Clinical Trial of Autologous CD22 Chimeric Antigen Receptor (CAR) T Cells in Adults With Recurrent or Refractory B Cell Malignancies

TypeinterventionalSponsorMatthew FrankRan2019 to 2025Enrolled52ConditionsB-ALL, B-cell Non Hodgkin Lymphoma, DLBCL, Follicular Lymphoma Grade 3BArmsFludarabine, Cyclophosphamide, CD22 CAR
NCT06735495 phase1 / phase2recruitingnot on this map

The Safety and Efficacy of CD19 & CD22 Bispecific CAR T Cells in Treating Relapsed / Refractory B Cell Hematological Tumors

TypeinterventionalSponsorUnion Hospital, Tongji Medical College, Huazhong University of Science and TechnologyRan2024 to 2027Enrolled80ConditionsB-Cell Lymphoblastic Leukemia/LymphomaArmsCD19&CD22 bispecific CAR-T cells
3 · Its place in the literature

Who cites it

45 citing papers in PubMed.

  1. Article
  2. Review
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  5. Article
  6. Review
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  8. CD22 as a Target for Hematological Malignancies and Autoimmune Diseases.International journal of molecular sciences · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Rational redesign of antigen binding domain improves in vivo efficacy of the CD22-CAR.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  17. Review
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  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Matthew J FrankDivision of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA. Electronic address: mjfrank@stanford.edu.
John H BairdDivision of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA.
Anne Marijn KramerDivision of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Cancer Center Amsterdam, Department of Hematology, Amsterdam University Medical Center, Amsterdam, Netherlands.
Hrishikesh K SrinageshDivision of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Shabnum PatelCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Annie Kathleen BrownCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Jean S OakDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Sheren F YounesDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Yasodha NatkunamDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Mark P HamiltonDivision of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Yi-Jiun SuDivision of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Division of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
Neha AgarwalDivision of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Harshini ChinnasamyCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Emily EgelerCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Sharon MavroukakisCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Steven A FeldmanCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Bita SahafCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Crystal L MackallDivision of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Lori MufflyCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
David B MiklosDivision of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA. Electronic address: dmiklos@stanford.edu.
CARdinal-22 Investigator group

Funding

TUMOR SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN BONE MARROW TRANSPLANTATIONP01CA049605 · NCI · STANFORD UNIVERSITY · PI David B. Miklos, Robert S Negrin · 1989 to 2026
$73.3M
Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI MICHAEL KENNEY · 2007 to 2026
$71.4M
PURPOSE OF THE NGVB CONTRACT IS TO CONTINUE SUPPORTING GENE THERAPY RESEARCH.75N92019D00018 · OD · INDIANA UNIVERSITY INDIANAPOLIS · 2019 to 2023
$1.7M
Lymphoma Antigen Density and Circulating Tumor DNA Profiling As Determinants of Novel CAR TherapiesK08CA248968 · NCI · STANFORD UNIVERSITY · PI FRANK, MATTHEW J. · 2020 to 2024
$845k
REGULATION OF THE BIOSYNTHESIS OF THE OPIOID PEPTIDES AND OTHER NEUROPEPTIDESZ01HL000018 · NHLBI · HEART, LUNG, AND BLOOD INSTITUTE · PI SABOL, S L · 1985 to 1992
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NCI NIH HHS K08 CA248968NCI NIH HHS P01 CA049605NCI NIH HHS P30 CA124435NHLBI NIH HHS 75N92019D00018
6 · The paper itself

Abstract

backgroundOutcomes are poor for patients with large B-cell lymphoma who relapse after CD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR19). CD22 is a nearly universally expressed B-cell surface antigen and the efficacy of a CD22-directed CAR T-cell therapy (CAR22) in large B-cell lymphoma is unknown, which was what we aimed to examine in this study.

methodsIn this single centre, open-label, dose-escalation phase 1 trial, we intravenously administered CAR22 at two dose levels (1 million and 3 million CAR22-positive T cells per kg of bodyweight) to adult patients (aged ≥18 years) who relapsed after CAR19 or had CD19-negative large B-cell lymphoma. The primary endpoints were manufacturing feasibility, safety measured by the incidence and severity of adverse events and dose-limiting toxicities, and identification of the maximum tolerated dose (ie, the recommended phase 2 dose). This study is registered with ClinicalTrials.gov (NCT04088890) and is active, but closed for enrolment.

findingsFrom Oct 17, 2019, to Oct 19, 2022, a total of 41 patients were assessed for eligibility; however, one patient withdrew. 40 patients underwent leukapheresis and 38 (95%) had CAR T-cell products manufactured successfully. The median age was 65 years (range 25-84), 17 (45%) were women, 32 (84%) had elevated pretreatment lactate dehydrogenase, 11 (29%) had refractory disease to all previous therapies, and patients had received a median of four lines of previous therapy (range 3-8). Of the 38 patients treated, 37 (97%) had relapsed after previous CAR19. The identified maximum tolerated dose was 1 million CAR T cells per kg. Of 29 patients who received the maximum tolerated dose, no patients developed a dose-limiting toxicity or grade 3 or higher cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or immune effector cell-associated haemophagocytic lymphohistiocytosis-like syndrome.

interpretationThis trial identifies CD22 as an immunotherapeutic target in large B-cell lymphoma and demonstrates the durable clinical activity of CAR22 in patients with disease progression after CAR19 therapy. Although these findings are promising, it is essential to recognise that this is a phase 1 dose-finding study. Further investigations are warranted to establish the long-term efficacy and to delineate the patient subgroups that will derive the most benefit from this therapeutic approach.

fundingNational Cancer Institute, National Institutes of Health, Stanford Cancer Institute, Leukemia & Lymphoma Society, Parker Institute for Cancer Immunotherapy, Lymph & Co, and the European Hematology Association.

Indexed as

Antigens, CD19Immunotherapy, AdoptiveSialic Acid Binding Ig-like Lectin 2AdultAgedAged, 80 and overFemaleHumansLymphoma, Large B-Cell, DiffuseMaleMaximum Tolerated DoseMiddle AgedReceptors, Chimeric AntigenAntigens, CD19CD22 protein, humanReceptors, Chimeric AntigenSialic Acid Binding Ig-like Lectin 2

Identifiers

PMID38996463
PMCPMC11329226

What Socratic holds

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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.